During the coronavirus disease 2019 pandemic, mathematical modeling has been widely used to understand epidemiological burden, trends, and transmission dynamics, to facilitate policy decisions, and, to a lesser extent, to evaluate infection prevention and control (IPC) measures. This review highlights the added value of using conventional epidemiology and modeling approaches to address the complexity of healthcare-associated infections (HAI) and antimicrobial resistance. It demonstrates how epidemiological surveillance data and modeling can be used to infer transmission dynamics in healthcare settings and to forecast healthcare impact, how modeling can be used to improve the validity of interpretation of epidemiological surveillance data, how modeling can be used to estimate the impact of IPC interventions, and how modeling can be used to guide IPC and antimicrobial treatment and stewardship decision-making. There are several priority areas for expanding the use of modeling in healthcare epidemiology and IPC. Importantly, modeling should be viewed as complementary to conventional healthcare epidemiological approaches, and this requires collaboration and active coordination between IPC, healthcare epidemiology, and mathematical modeling groups.

BACKGROUND: The majority of recent estimates on the direct medical cost attributable to hospital-onset infections (HOIs) has focused on device- or procedure-associated HOIs. The attributable costs of HOIs that are not associated with device use or procedures have not been extensively studied. OBJECTIVE: We developed simulation models of attributable cost for 16 HOIs and estimated the total direct medical cost, including nondevice-related HOIs in the USA for 2011 and 2015. DATA AND METHODS: We used total discharge costs associated with HOI-related hospitalization from the National Inpatient Sample and applied an analogy costing methodology to develop simulation models of the costs attributable to HOIs. The mean attributable cost estimate from the simulation analysis was then multiplied by previously published estimates of the number of HOIs for 2011 and 2015 to generate national estimates of direct medical costs. RESULTS: After adjusting all estimates to 2017 US dollars, attributable cost estimates for select nondevice-related infections attributable cost estimates ranged from $7661 for ear, eye, nose, throat, and mouth (EENTM) infections to $27,709 for cardiovascular system infections in 2011; and from $8394 for EENTM to $26,445 for central nervous system infections in 2016 (based on 2015 incidence data). The national direct medical costs for all HOIs were $14.6 billion in 2011 and $12.1 billion in 2016. Nondevice- and nonprocedure-associated HOIs comprise approximately 26-28% of total HOI costs. CONCLUSION: Results suggest that nondevice- and nonprocedure-related HOIs result in considerable costs to the healthcare system.

BACKGROUND: Detection and containment of hospital outbreaks currently depend on variable and personnel-intensive surveillance methods. Whether automated statistical surveillance for outbreaks of health care-associated pathogens allows earlier containment efforts that would reduce the size of outbreaks is unknown. METHODS: We conducted a cluster-randomized trial in 82 community hospitals within a larger health care system. All hospitals followed an outbreak response protocol when outbreaks were detected by their infection prevention programs. Half of the hospitals additionally used statistical surveillance of microbiology data, which alerted infection prevention programs to outbreaks. Statistical surveillance was also applied to microbiology data from control hospitals without alerting their infection prevention programs. The primary outcome was the number of additional cases occurring after outbreak detection. Analyses assessed differences between the intervention period (July 2019 to January 2022) versus baseline period (February 2017 to January 2019) between randomized groups. A post hoc analysis separately assessed pre-coronavirus disease 2019 (Covid-19) and Covid-19 pandemic intervention periods. RESULTS: Real-time alerts did not significantly reduce the number of additional outbreak cases (intervention period versus baseline: statistical surveillance relative rate [RR]=1.41, control RR=1.81; difference-in-differences, 0.78; 95% confidence interval [CI], 0.40 to 1.52; P=0.46). Comparing only the prepandemic intervention with baseline periods, the statistical outbreak surveillance group was associated with a 64.1% reduction in additional cases (statistical surveillance RR=0.78, control RR=2.19; difference-in-differences, 0.36; 95% CI, 0.13 to 0.99). There was no similarly observed association between the pandemic versus baseline periods (statistical surveillance RR=1.56, control RR=1.66; difference-in-differences, 0.94; 95% CI, 0.46 to 1.92). CONCLUSIONS: Automated detection of hospital outbreaks using statistical surveillance did not reduce overall outbreak size in the context of an ongoing pandemic. (Funded by the Centers for Disease Control and Prevention; ClinicalTrials.gov number, NCT04053075. Support for HCA Healthcare's participation in the study was provided in kind by HCA.).

IMPORTANCE: Pneumonia is the most common infection requiring hospitalization and is a major reason for overuse of extended-spectrum antibiotics. Despite low risk of multidrug-resistant organism (MDRO) infection, clinical uncertainty often drives initial antibiotic selection. Strategies to limit empiric antibiotic overuse for patients with pneumonia are needed. OBJECTIVE: To evaluate whether computerized provider order entry (CPOE) prompts providing patient- and pathogen-specific MDRO infection risk estimates could reduce empiric extended-spectrum antibiotics for non-critically ill patients admitted with pneumonia. DESIGN, SETTING, AND PARTICIPANTS: Cluster-randomized trial in 59 US community hospitals comparing the effect of a CPOE stewardship bundle (education, feedback, and real-time MDRO risk-based CPOE prompts; n = 29 hospitals) vs routine stewardship (n = 30 hospitals) on antibiotic selection during the first 3 hospital days (empiric period) in non-critically ill adults (≥18 years) hospitalized with pneumonia. There was an 18-month baseline period from April 1, 2017, to September 30, 2018, and a 15-month intervention period from April 1, 2019, to June 30, 2020. INTERVENTION: CPOE prompts recommending standard-spectrum antibiotics in patients ordered to receive extended-spectrum antibiotics during the empiric period who have low estimated absolute risk (<10%) of MDRO pneumonia, coupled with feedback and education. MAIN OUTCOMES AND MEASURES: The primary outcome was empiric (first 3 days of hospitalization) extended-spectrum antibiotic days of therapy. Secondary outcomes included empiric vancomycin and antipseudomonal days of therapy and safety outcomes included days to intensive care unit (ICU) transfer and hospital length of stay. Outcomes compared differences between baseline and intervention periods across strategies. RESULTS: Among 59 hospitals with 96 451 (51 671 in the baseline period and 44 780 in the intervention period) adult patients admitted with pneumonia, the mean (SD) age of patients was 68.1 (17.0) years, 48.1% were men, and the median (IQR) Elixhauser comorbidity count was 4 (2-6). Compared with routine stewardship, the group using CPOE prompts had a 28.4% reduction in empiric extended-spectrum days of therapy (rate ratio, 0.72 [95% CI, 0.66-0.78]; P < .001). Safety outcomes of mean days to ICU transfer (6.5 vs 7.1 days) and hospital length of stay (6.8 vs 7.1 days) did not differ significantly between the routine and CPOE intervention groups. CONCLUSIONS AND RELEVANCE: Empiric extended-spectrum antibiotic use was significantly lower among adults admitted with pneumonia to non-ICU settings in hospitals using education, feedback, and CPOE prompts recommending standard-spectrum antibiotics for patients at low risk of MDRO infection, compared with routine stewardship practices. Hospital length of stay and days to ICU transfer were unchanged. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03697070.

IMPORTANCE: Urinary tract infection (UTI) is the second most common infection leading to hospitalization and is often associated with gram-negative multidrug-resistant organisms (MDROs). Clinicians overuse extended-spectrum antibiotics although most patients are at low risk for MDRO infection. Safe strategies to limit overuse of empiric antibiotics are needed. OBJECTIVE: To evaluate whether computerized provider order entry (CPOE) prompts providing patient- and pathogen-specific MDRO risk estimates could reduce use of empiric extended-spectrum antibiotics for treatment of UTI. DESIGN, SETTING, AND PARTICIPANTS: Cluster-randomized trial in 59 US community hospitals comparing the effect of a CPOE stewardship bundle (education, feedback, and real-time and risk-based CPOE prompts; 29 hospitals) vs routine stewardship (n = 30 hospitals) on antibiotic selection during the first 3 hospital days (empiric period) in noncritically ill adults (≥18 years) hospitalized with UTI with an 18-month baseline (April 1, 2017-September 30, 2018) and 15-month intervention period (April 1, 2019-June 30, 2020). INTERVENTIONS: CPOE prompts recommending empiric standard-spectrum antibiotics in patients ordered to receive extended-spectrum antibiotics who have low estimated absolute risk (<10%) of MDRO UTI, coupled with feedback and education. MAIN OUTCOMES AND MEASURES: The primary outcome was empiric (first 3 days of hospitalization) extended-spectrum antibiotic days of therapy. Secondary outcomes included empiric vancomycin and antipseudomonal days of therapy. Safety outcomes included days to intensive care unit (ICU) transfer and hospital length of stay. Outcomes were assessed using generalized linear mixed-effect models to assess differences between the baseline and intervention periods. RESULTS: Among 127 403 adult patients (71 991 baseline and 55 412 intervention period) admitted with UTI in 59 hospitals, the mean (SD) age was 69.4 (17.9) years, 30.5% were male, and the median Elixhauser Comorbidity Index count was 4 (IQR, 2-5). Compared with routine stewardship, the group using CPOE prompts had a 17.4% (95% CI, 11.2%-23.2%) reduction in empiric extended-spectrum days of therapy (rate ratio, 0.83 [95% CI, 0.77-0.89]; P < .001). The safety outcomes of mean days to ICU transfer (6.6 vs 7.0 days) and hospital length of stay (6.3 vs 6.5 days) did not differ significantly between the routine and intervention groups, respectively. CONCLUSIONS AND RELEVANCE: Compared with routine stewardship, CPOE prompts providing real-time recommendations for standard-spectrum antibiotics for patients with low MDRO risk coupled with feedback and education significantly reduced empiric extended-spectrum antibiotic use among noncritically ill adults admitted with UTI without changing hospital length of stay or days to ICU transfers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03697096.

IMPORTANCE: Infections due to multidrug-resistant organisms (MDROs) are associated with increased morbidity, mortality, length of hospitalization, and health care costs. Regional interventions may be advantageous in mitigating MDROs and associated infections. OBJECTIVE: To evaluate whether implementation of a decolonization collaborative is associated with reduced regional MDRO prevalence, incident clinical cultures, infection-related hospitalizations, costs, and deaths. DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study was conducted from July 1, 2017, to July 31, 2019, across 35 health care facilities in Orange County, California. EXPOSURES: Chlorhexidine bathing and nasal iodophor antisepsis for residents in long-term care and hospitalized patients in contact precautions (CP). MAIN OUTCOMES AND MEASURES: Baseline and end of intervention MDRO point prevalence among participating facilities; incident MDRO (nonscreening) clinical cultures among participating and nonparticipating facilities; and infection-related hospitalizations and associated costs and deaths among residents in participating and nonparticipating nursing homes (NHs). RESULTS: Thirty-five facilities (16 hospitals, 16 NHs, 3 long-term acute care hospitals [LTACHs]) adopted the intervention. Comparing decolonization with baseline periods among participating facilities, the mean (SD) MDRO prevalence decreased from 63.9% (12.2%) to 49.9% (11.3%) among NHs, from 80.0% (7.2%) to 53.3% (13.3%) among LTACHs (odds ratio [OR] for NHs and LTACHs, 0.48; 95% CI, 0.40-0.57), and from 64.1% (8.5%) to 55.4% (13.8%) (OR, 0.75; 95% CI, 0.60-0.93) among hospitalized patients in CP. When comparing decolonization with baseline among NHs, the mean (SD) monthly incident MDRO clinical cultures changed from 2.7 (1.9) to 1.7 (1.1) among participating NHs, from 1.7 (1.4) to 1.5 (1.1) among nonparticipating NHs (group × period interaction reduction, 30.4%; 95% CI, 16.4%-42.1%), from 25.5 (18.6) to 25.0 (15.9) among participating hospitals, from 12.5 (10.1) to 14.3 (10.2) among nonparticipating hospitals (group × period interaction reduction, 12.9%; 95% CI, 3.3%-21.5%), and from 14.8 (8.6) to 8.2 (6.1) among LTACHs (all facilities participating; 22.5% reduction; 95% CI, 4.4%-37.1%). For NHs, the rate of infection-related hospitalizations per 1000 resident-days changed from 2.31 during baseline to 1.94 during intervention among participating NHs, and from 1.90 to 2.03 among nonparticipating NHs (group × period interaction reduction, 26.7%; 95% CI, 19.0%-34.5%). Associated hospitalization costs per 1000 resident-days changed from $64 651 to $55 149 among participating NHs and from $55 151 to $59 327 among nonparticipating NHs (group × period interaction reduction, 26.8%; 95% CI, 26.7%-26.9%). Associated hospitalization deaths per 1000 resident-days changed from 0.29 to 0.25 among participating NHs and from 0.23 to 0.24 among nonparticipating NHs (group × period interaction reduction, 23.7%; 95% CI, 4.5%-43.0%). CONCLUSIONS AND RELEVANCE: A regional collaborative involving universal decolonization in long-term care facilities and targeted decolonization among hospital patients in CP was associated with lower MDRO carriage, infections, hospitalizations, costs, and deaths.

IMPORTANCE: Universal nasal mupirocin plus chlorhexidine gluconate (CHG) bathing in intensive care units (ICUs) prevents methicillin-resistant Staphylococcus aureus (MRSA) infections and all-cause bloodstream infections. Antibiotic resistance to mupirocin has raised questions about whether an antiseptic could be advantageous for ICU decolonization. OBJECTIVE: To compare the effectiveness of iodophor vs mupirocin for universal ICU nasal decolonization in combination with CHG bathing. DESIGN, SETTING, AND PARTICIPANTS: Two-group noninferiority, pragmatic, cluster-randomized trial conducted in US community hospitals, all of which used mupirocin-CHG for universal decolonization in ICUs at baseline. Adult ICU patients in 137 randomized hospitals during baseline (May 1, 2015-April 30, 2017) and intervention (November 1, 2017-April 30, 2019) were included. INTERVENTION: Universal decolonization involving switching to iodophor-CHG (intervention) or continuing mupirocin-CHG (baseline). MAIN OUTCOMES AND MEASURES: ICU-attributable S aureus clinical cultures (primary outcome), MRSA clinical cultures, and all-cause bloodstream infections were evaluated using proportional hazard models to assess differences from baseline to intervention periods between the strategies. Results were also compared with a 2009-2011 trial of mupirocin-CHG vs no decolonization in the same hospital network. The prespecified noninferiority margin for the primary outcome was 10%. RESULTS: Among the 801 668 admissions in 233 ICUs, the participants' mean (SD) age was 63.4 (17.2) years, 46.3% were female, and the mean (SD) ICU length of stay was 4.8 (4.7) days. Hazard ratios (HRs) for S aureus clinical isolates in the intervention vs baseline periods were 1.17 for iodophor-CHG (raw rate: 5.0 vs 4.3/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 4.1 vs 4.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 18.4% [95% CI, 10.7%-26.6%] for mupirocin-CHG, P < .001). For MRSA clinical cultures, HRs were 1.13 for iodophor-CHG (raw rate: 2.3 vs 2.1/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 2.0 vs 2.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 14.1% [95% CI, 3.7%-25.5%] for mupirocin-CHG, P = .007). For all-pathogen bloodstream infections, HRs were 1.00 (2.7 vs 2.7/1000) for iodophor-CHG and 1.01 (2.6 vs 2.6/1000) for mupirocin-CHG (nonsignificant HR difference in differences, -0.9% [95% CI, -9.0% to 8.0%]; P = .84). Compared with the 2009-2011 trial, the 30-day relative reduction in hazards in the mupirocin-CHG group relative to no decolonization (2009-2011 trial) were as follows: S aureus clinical cultures (current trial: 48.1% [95% CI, 35.6%-60.1%]; 2009-2011 trial: 58.8% [95% CI, 47.5%-70.7%]) and bloodstream infection rates (current trial: 70.4% [95% CI, 62.9%-77.8%]; 2009-2011 trial: 60.1% [95% CI, 49.1%-70.7%]). CONCLUSIONS AND RELEVANCE: Nasal iodophor antiseptic did not meet criteria to be considered noninferior to nasal mupirocin antibiotic for the outcome of S aureus clinical cultures in adult ICU patients in the context of daily CHG bathing. In addition, the results were consistent with nasal iodophor being inferior to nasal mupirocin. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03140423.

IMPORTANCE: Characterizing the scale and factors associated with hospital-onset SARS-CoV-2 infections could help inform hospital and public health policies regarding prevention and surveillance needs for these infections. OBJECTIVE: To evaluate associations of hospital-onset SARS-CoV-2 infection rates with different periods of the COVID-19 pandemic, hospital characteristics, and testing practices. DESIGN, SETTING, AND PARTICIPANTS: This cohort study of US hospitals reporting SARS-CoV-2 testing data in the PINC AI Healthcare Database COVID-19 special release files was conducted from July 2020 through June 2022. Data were collected from hospitals that reported at least 1 SARS-CoV-2 reverse transcription-polymerase chain reaction or antigen test during hospitalizations discharged that month. For each hospital-month where the hospital reported sufficient data, all hospitalizations discharged in that month were included in the cohort. SARS-CoV-2 viral tests and results reported in the microbiology files for all hospitalizations in the study period by discharge month were identified. Data analysis was conducted from September 2022 to March 2023. EXPOSURE: Hospitalizations discharged in an included hospital-month. MAIN OUTCOMES AND MEASURES: Multivariable generalized estimating equation negative-binomial regression models were used to assess associations of monthly rates of hospital-onset SARS-CoV-2 infections per 1000 patient-days (defined as a first positive SARS-CoV-2 test during after hospitalization day 7) with the phase of the pandemic (defined as the predominant SARS-CoV-2 variant in circulation), admission testing rates, and hospital characteristics (hospital bed size, teaching status, urban vs rural designation, Census region, and patient distribution variables). RESULTS: A total of 5687 hospital-months from 288 distinct hospitals were included, which contributed 4 421 268 hospitalization records. Among 171 564 hospitalizations with a positive SARS-CoV-2 test, 7591 (4.4%) were found to be hospital onset and 6455 (3.8%) were indeterminate onset. The mean monthly hospital-onset infection rate per 1000 patient-days was 0.27 (95 CI, 0.26-0.29). Hospital-onset infections occurred in 2217 of 5687 hospital-months (39.0%). The monthly percentage of discharged patients tested for SARS-CoV-2 at admission varied; 1673 hospital-months (29.4%) had less than 25% of hospitalizations tested at admission; 2199 hospital-months (38.7%) had 25% to 50% of all hospitalizations tested, and 1815 hospital months (31.9%) had more than 50% of all hospitalizations tested at admission. Postadmission testing rates and community-onset infection rates increased with admission testing rates. In multivariable models restricted to hospital-months testing at least 25% of hospitalizations at admission, a 10% increase in community-onset SARS-CoV-2 infection rate was associated with a 178% increase in the hospital-onset infection rate (rate ratio, 2.78; 95% CI, 2.52-3.07). Additionally, the phase of the COVID-19 pandemic, the admission testing rate, Census region, and bed size were all significantly associated with hospital-onset SARS-CoV-2 infection rates. CONCLUSIONS AND RELEVANCE: In this cohort study of hospitals reporting SARS-CoV-2 infections, there was an increase of hospital-onset SARS-CoV-2 infections when community-onset infections were higher, indicating a need for ongoing and enhanced surveillance and prevention efforts to reduce in-hospital transmission of SARS-CoV-2 infections, particularly when community-incidence of SARS-CoV-2 infections is high.

Background SARS-CoV-2 outbreaks in nursing homes can be large with high case fatality. Identifying asymptomatic individuals early through serial testing is recommended to control COVID-19 in nursing homes, both in response to an outbreak (“outbreak testing” of residents and healthcare personnel) and in facilities without outbreaks (“non-outbreak testing” of healthcare personnel). The effectiveness of outbreak testing and isolation with or without non-outbreak testing was evaluated.Methods Using published SARS-CoV-2 transmission parameters, the fraction of SARS-CoV-2 transmissions prevented through serial testing (weekly, every three days, or daily) and isolation of asymptomatic persons compared to symptom-based testing and isolation was evaluated through mathematical modeling using a Reed-Frost model to estimate the percentage of cases prevented (i.e., “effectiveness”) through either outbreak testing alone or outbreak plus non-outbreak testing. The potential effect of simultaneous decreases (by 10%) in the effectiveness of isolating infected individuals when instituting testing strategies was also evaluated.Results Modeling suggests that outbreak testing could prevent 54% (weekly testing with 48-hour test turnaround) to 92% (daily testing with immediate results and 50% relative sensitivity) of SARS-CoV-2 infections. Adding non-outbreak testing could prevent up to an additional 8% of SARS-CoV-2 infections (depending on test frequency and turnaround time). However, added benefits of non-outbreak testing were mostly negated if accompanied by decreases in infection control practice.Conclusions When combined with high-quality infection control practices, outbreak testing could be an effective approach to preventing COVID-19 in nursing homes, particularly if optimized through increased test frequency and use of tests with rapid turnaround.Summary Mathematical modeling evaluated the effectiveness of serially testing asymptomatic persons in a nursing home in response to a SARS-CoV-2 outbreak with or without serial testing of asymptomatic staff in the absence of known SARS-CoV-2 infections.Competing Interest StatementThe authors have declared no competing interest.Funding StatementNo external funding was received. All work was conducted as part of government duties.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy (see e.g., 45 C.F.R. part 46, 21 C.F.R. part 56; 42 U.S.C. 241(d); 5 U.S.C 552a; 44 U.S.C. 351 et seq.).All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData provided in supplemental materials or publicly available through links in the manuscript. https://github.com/cdcepi/Nursing-home-SARS-CoV-2-testing-model/

Importance: There are limited data describing SARS-CoV-2-specific immune responses and their durability following infection and vaccination in nursing home residents. Objective(s): To evaluate the quantitative titers and durability of binding antibodies detected after SARSCoV-2 infection and subsequent COVID-19 vaccination. Design(s): A prospective longitudinal evaluation included nine visits over 150 days; visits included questionnaire administration, blood collection for serology, and paired anterior nasal specimen collection for testing by BinaxNOWTM COVID-19 Ag Card (BinaxNOW), reverse transcription polymerase chain reaction (RT-PCR), and viral culture. Setting(s): A nursing home during and after a SARS-CoV-2 outbreak. Participant(s): 11 consenting SARS-CoV-2-positive nursing home residents. Main Outcomes and Measures: SARS-CoV-2 testing (BinaxNOWTM, RT-PCR, viral culture); quantitative titers of binding SARS-CoV-2 antibodies post-infection and post-vaccination (beginning after the first dose of the primary series). Result(s): 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. Conclusions and Relevance: 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. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

One in six nursing home residents and staff with positive SARS-CoV-2 tests 90 days after initial infection had specimen cycle thresholds (Ct) <30. Individuals with specimen Ct<30 were more likely to report symptoms but were not different from individuals with high Ct value specimens by other clinical and testing data.

The authors reply: We thank Calbo and colleagues for highlighting the need to better understand the role of asymptomatic shedding in transmission of SARS-CoV-2 in health care settings. Our study focused on transmission of SARS-CoV-2 from asymptomatic and presymptomatic residents in a skilled nursing facility. As we noted, health care personnel with undetected infection probably contributed to transmission in this facility, but we could not document this because we were unable to test asymptomatic health care personnel as part of this investigation owing to limited testing resources at the time. Since that investigation, the CDC has provided guidance on testing strategies in nursing homes.1 In addition, the CDC recommends universal source control in all health care settings to help prevent transmission from health care personnel with unrecognized SARS-CoV-2 infection.2 | | The data provided by Calbo et al. suggest important hypotheses about the role of patients and health care personnel with asymptomatic SARS-CoV-2 infection in ongoing transmission in acute care facilities, a setting that is distinct from the residential skilled nursing facility described in our article. Further studies may help to better quantify the benefit of active surveillance (including laboratory testing) when added to active symptom screening and universal source control in various health care settings.

SARS-CoV-2 infections among vaccinated nursing home residents increased after the Omicron variant emerged. Data on booster dose effectiveness in this population are limited. During July 2021-March 2022, nursing home outbreaks in 11 US jurisdictions involving >3 infections within 14 days among residents who had received at least the primary COVID-19 vaccine(s) were monitored. Among 2,188 nursing homes, 1,247 outbreaks were reported in the periods of Delta (n = 356, 29%), mixed Delta/Omicron (n = 354, 28%), and Omicron (n = 536, 43%) predominance. During the Omicron-predominant period, the risk for infection within 14 days of an outbreak start was lower among boosted residents than among residents who had received the primary vaccine series alone (risk ratio [RR] 0.25, 95% CI 0.19-0.33). Once infected, boosted residents were at lower risk for all-cause hospitalization (RR 0.48, 95% CI 0.40-0.49) and death (RR 0.45, 95% CI 0.34-0.59) than primary vaccine-only residents.

BACKGROUND: Descriptions of changes in invasive bacterial disease (IBD) epidemiology during the COVID-19 pandemic in the United States are limited. METHODS: We investigated changes in the incidence of IBD due to Streptococcus pneumoniae, Haemophilus influenzae, group A Streptococcus (GAS), and group B Streptococcus (GBS). We defined the COVID-19 pandemic period as March 1-December 31, 2020. We compared observed IBD incidences during the pandemic to expected incidences, consistent with January 2014-February 2020 trends. We conducted secondary analysis of a healthcare database to assess changes in testing by blood and cerebrospinal fluid (CSF) culture during the pandemic. RESULTS: Compared with expected incidences, the observed incidences of IBD due to S. pneumoniae, H. influenzae, GAS, and GBS were 58%, 60%, 28%, and 12% lower during the pandemic period of 2020, respectively. Declines from expected incidences corresponded closely with implementation of COVID-19-associated non-pharmaceutical-interventions (NPIs). Significant declines were observed across all age, race groups and surveillance sites for S pneumoniae and H influenzae. Blood and CSF culture testing rates during the pandemic were comparable to previous years. CONCLUSIONS: NPIs likely contributed to the decline in IBD incidence in the United States in 2020; observed declines were unlikely to be driven by reductions in testing.

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).

Among nursing home outbreaks of coronavirus disease 2019 (COVID-19) with ≥3 breakthrough infections when the predominant severe acute respiratory coronavirus virus 2 (SARS-CoV-2) variant circulating was the SARS-CoV-2 δ (delta) variant, fully vaccinated residents were 28% less likely to be infected than were unvaccinated residents. Once infected, they had approximately half the risk for all-cause hospitalization and all-cause death compared with unvaccinated infected residents.

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.

A SARS-CoV-2 P.1 (Gamma) variant outbreak occurred at a skilled nursing facility in Washington, USA, in April 2021. Effectiveness of 2 doses of mRNA vaccines against P.1 infection among residents in this outbreak was 75.0% (95% CI 44.5%-88.7%), similar to effectiveness for other pre-Delta variants among long-term care residents.

Nursing home residents continue to experience significant COVID-19 morbidity and mortality (1). On March 29, 2022, the Advisory Committee on Immunization Practices (ACIP) recommended a second mRNA COVID-19 vaccine booster dose for adults aged ≥50 years and all immunocompromised persons who had received a first booster ≥4 months earlier.* On September 1, 2022, ACIP voted to recommend bivalent mRNA COVID-19 vaccine boosters for all persons aged ≥12 years who had completed the primary series using monovalent vaccines ≥2 months earlier (2). Data on COVID-19 booster dose vaccine effectiveness (VE) in the nursing home population are limited (3). For this analysis, academic, federal, and private partners evaluated routine care data collected from 196 U.S. community nursing homes to estimate VE of a second mRNA COVID-19 vaccine booster dose among nursing home residents who had received 3 previous COVID-19 vaccine doses (2 primary series doses and 1 booster dose). Residents who received second mRNA COVID-19 vaccine booster doses during March 29-June 15, 2022, with follow-up through July 25, 2022, were found to have 60-day VE of 25.8% against SARS-CoV-2 (the virus that causes COVID-19 infection), 73.9% against severe COVID-19 outcomes (a combined endpoint of COVID-19-associated hospitalizations or deaths), and 89.6% against COVID-19-associated deaths alone. During this period, subvariants BA.2 and BA.2.12.1 (March-June 2022), and BA.4 and BA.5 (July 2022) of the B.1.1.529 and BA.2 (Omicron) variant were predominant. These findings suggest that among nursing home residents, second mRNA COVID-19 vaccine booster doses provided additional protection over first booster doses against severe COVID-19 outcomes during a time of emerging Omicron variants. Facilities should continue to ensure that nursing home residents remain up to date with COVID-19 vaccination, including bivalent vaccine booster doses, to prevent severe COVID-19 outcomes.

The disruptions of the coronavirus disease 2019 (COVID-19) pandemic impacted the delivery and utilization of healthcare services with potential long-term implications for population health and the hospital workforce. Using electronic health record data from over 700 USacute care hospitals, we documented changes in admissions to hospital service areas (inpatient, observation, emergency room [ER], and same-day surgery) during 2019-2020 and examined whether surges of COVID-19 hospitalizations corresponded with increased inpatient disease severity and death rate. We found that in 2020, hospitalizations declined by 50% in April, with greatest declines occurring in same-day surgery (-73%). The youngest patients (0-17) experienced largest declines in ER, observation, and same-day surgery admissions; inpatient admissions declined the most among the oldest patients (65+). Infectious disease admissions increased by 52%. The monthly measures of inpatient case mix index, length of stay, and non-COVID death rate were higher in all months in 2020 compared with respective months in 2019.

We described bacterial/fungal co-infections and antibiotic resistant infections among inpatients diagnosed with COVID-19 and compared findings with inpatients diagnosed with influenza-like-illness. Less than 10% of COVID-19 inpatients had bacterial/fungal co-infection. Longer lengths of stay, critical care stay, and mechanical ventilation contribute to increased incidence of hospital-onset infections among COVID-19 inpatients.

OBJECTIVES: The coronavirus disease 2019 pandemic caused substantial changes to healthcare delivery and antibiotic prescribing beginning in March 2020. To assess pandemic impact on Clostridioides difficile infection (CDI) rates, we described patients and trends in facility-level incidence, testing rates, and percent positivity during 2019-2020 in a large cohort of US hospitals. METHODS: We estimated and compared rates of community-onset CDI (CO-CDI) per 10,000 discharges, hospital-onset CDI (HO-CDI) per 10,000 patient days, and C. difficile testing rates per 10,000 discharges in 2019 and 2020. We calculated percent positivity as the number of inpatients diagnosed with CDI over the total number of discharges with a test for C. difficile. We used an interrupted time series (ITS) design with negative binomial and logistic regression models to describe level and trend changes in rates and percent positivity before and after March 2020. RESULTS: In pairwise comparisons, overall CO-CDI rates decreased from 20.0 to 15.8 between 2019 and 2020 (P < .0001). HO-CDI rates did not change. Using ITS, we detected decreasing monthly trends in CO-CDI (-1% per month, P = .0036) and HO-CDI incidence (-1% per month, P < .0001) during the baseline period, prior to the COVID-19 pandemic declaration. We detected no change in monthly trends for CO-CDI or HO-CDI incidence or percent positivity after March 2020 compared with the baseline period. CONCLUSIONS: While there was a slight downward trajectory in CDI trends prior to March 2020, no significant change in CDI trends occurred during the COVID-19 pandemic despite changes in infection control practices, antibiotic use, and healthcare delivery.

During July-August 2021, a COVID-19 outbreak involving 21 residents (all fully vaccinated) and 10 staff (9 fully vaccinated) occurred in a Connecticut nursing home. The outbreak was likely initiated by a fully vaccinated staff member and propagated by fully vaccinated persons. Prior COVID-19 was protective among vaccinated residents.

Nursing home and long-term care facility residents live in congregate settings and are often elderly and frail, putting them at high risk for infection with SARS-CoV-2, the virus that causes COVID-19, and severe COVID-19-associated outcomes; therefore, this population was prioritized for early vaccination in the United States (1). Following rapid distribution and administration of the mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna) under an Emergency Use Authorization by the Food and Drug Administration (2), observational studies among nursing home residents demonstrated vaccine effectiveness (VE) ranging from 53% to 92% against SARS-CoV-2 infection (3-6). However, concerns about the potential for waning vaccine-induced immunity and the recent emergence of the highly transmissible SARS-CoV-2 B.1.617.2 (Delta) variant(†) highlight the need to continue to monitor VE (7). Weekly data reported by the Centers for Medicaid & Medicare (CMS)-certified skilled nursing facilities or nursing homes to CDC's National Healthcare Safety Network (NHSN)(§) were analyzed to evaluate effectiveness of full vaccination (2 doses received ≥14 days earlier) with any of the two currently authorized mRNA COVID-19 vaccines during the period soon after vaccine introduction and before the Delta variant was circulating (pre-Delta [March 1-May 9, 2021]), and when the Delta variant predominated(¶) (Delta [June 21-August 1, 2021]). Using 17,407 weekly reports from 3,862 facilities from the pre-Delta period, adjusted effectiveness against infection for any mRNA vaccine was 74.7% (95% confidence interval [CI] = 70.0%-78.8%). Analysis using 33,160 weekly reports from 11,581 facilities during an intermediate period (May 10-June 20) found that the adjusted effectiveness was 67.5% (95% CI = 60.1%-73.5%). Analysis using 85,593 weekly reports from 14,917 facilities during the Delta period found that the adjusted effectiveness was 53.1% (95% CI = 49.1%-56.7%). Effectiveness estimates were similar for Pfizer-BioNTech and Moderna vaccines. These findings indicate that mRNA vaccines provide protection against SARS-CoV-2 infection among nursing home residents; however, VE was lower after the Delta variant became the predominant circulating strain in the United States. This analysis assessed VE against any infection, without being able to distinguish between asymptomatic and symptomatic presentations. Additional evaluations are needed to understand protection against severe disease in nursing home residents over time. Because nursing home residents might remain at some risk for SARS-CoV-2 infection despite vaccination, multiple COVID-19 prevention strategies, including infection control, testing, and vaccination of nursing home staff members, residents, and visitors, are critical. An additional dose of COVID-19 vaccine might be considered for nursing home and long-term care facility residents to optimize a protective immune response.

Replication-competent virus has not been detected in individuals with mild to moderate COVID-19 more than 10 days after symptom onset. It is unknown whether these findings apply to nursing home residents. Of 273 specimens collected from nursing home residents >10 days from the initial positive test, none were culture positive.

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.

BACKGROUND: To address high COVID-19 burden in U.S. nursing homes, rapid SARS-CoV-2 antigen tests have been widely distributed in those facilities. However, performance data are lacking, especially in asymptomatic people. OBJECTIVE: To evaluate the performance of SARS-CoV-2 antigen testing when used for facility-wide testing during a nursing home outbreak. DESIGN: A prospective evaluation involving 3 facility-wide rounds of testing where paired respiratory specimens were collected to evaluate the performance of the BinaxNOW antigen test compared with virus culture and real-time reverse transcription polymerase chain reaction (RT-PCR). Early and late infection were defined using changes in RT-PCR cycle threshold values and prior test results. SETTING: A nursing home with an ongoing SARS-CoV-2 outbreak. PARTICIPANTS: 532 paired specimens collected from 234 available residents and staff. MEASUREMENTS: Percentage of positive agreement (PPA) and percentage of negative agreement (PNA) for BinaxNOW compared with RT-PCR and virus culture. RESULTS: BinaxNOW PPA with virus culture, used for detection of replication-competent virus, was 95%. However, the overall PPA of antigen testing with RT-PCR was 69%, and PNA was 98%. When only the first positive test result was analyzed for each participant, PPA of antigen testing with RT-PCR was 82% among 45 symptomatic people and 52% among 343 asymptomatic people. Compared with RT-PCR and virus culture, the BinaxNOW test performed well in early infection (86% and 95%, respectively) and poorly in late infection (51% and no recovered virus, respectively). LIMITATION: Accurate symptom ascertainment was challenging in nursing home residents; test performance may not be representative of testing done by nonlaboratory staff. CONCLUSION: Despite lower positive agreement compared with RT-PCR, antigen test positivity had higher agreement with shedding of replication-competent virus. These results suggest that antigen testing could be a useful tool to rapidly identify contagious people at risk for transmitting SARS-CoV-2 during nascent outbreaks and help reduce COVID-19 burden in nursing homes. PRIMARY FUNDING SOURCE: None.

Residents of long-term care facilities (LTCFs), particularly those in skilled nursing facilities (SNFs), have experienced disproportionately high levels of COVID-19-associated morbidity and mortality and were prioritized for early COVID-19 vaccination (1,2). However, this group was not included in COVID-19 vaccine clinical trials, and limited postauthorization vaccine effectiveness (VE) data are available for this critical population (3). It is not known how well COVID-19 vaccines protect SNF residents, who typically are more medically frail, are older, and have more underlying medical conditions than the general population (1). In addition, immunogenicity of the Pfizer-BioNTech vaccine was found to be lower in adults aged 65-85 years than in younger adults (4). Through the CDC Pharmacy Partnership for Long-Term Care Program, SNF residents and staff members in Connecticut began receiving the Pfizer-BioNTech COVID-19 vaccine on December 18, 2020 (5). Administration of the vaccine was conducted during several on-site pharmacy clinics. In late January 2021, the Connecticut Department of Public Health (CT DPH) identified two SNFs experiencing COVID-19 outbreaks among residents and staff members that occurred after each facility's first vaccination clinic. CT DPH, in partnership with CDC, performed electronic chart review in these facilities to obtain information on resident vaccination status and infection with SARS-CoV-2, the virus that causes COVID-19. Partial vaccination, defined as the period from >14 days after the first dose through 7 days after the second dose, had an estimated effectiveness of 63% (95% confidence interval [CI] = 33%-79%) against SARS-CoV-2 infection (regardless of symptoms) among residents within these SNFs. This is similar to estimated effectiveness for a single dose of the Pfizer-BioNTech COVID-19 vaccine in adults across a range of age groups in noncongregate settings (6) and suggests that to optimize vaccine impact among this population, high coverage with the complete 2-dose series should be recommended for SNF residents and staff members.

BACKGROUND: Effective halting of outbreaks in skilled nursing facilities (SNFs) depends on the earliest recognition of cases. We assessed confirmed COVID-19 cases at an SNF impacted by COVID-19 in the United States to identify early indications of COVID-19 infection. METHODS: We performed retrospective reviews of electronic health records for residents with laboratory-confirmed SARS-CoV-2 during February 28-March 16, 2020. Records were abstracted for comorbidities, signs and symptoms, and illness outcomes during the 2 weeks before and after the date of positive specimen collection. Relative risks (RRs) of hospitalization and death were calculated. RESULTS: Of the 118 residents tested among approximately 130 residents from Facility A during February 28-March 16, 2020, 101 (86%) were found to test positive for SARS-CoV-2. At initial presentation, about two-thirds of SARS-CoV-2-positive residents had an abnormal vital sign or change in oxygen status. Most (90.2%) symptomatic residents had elevated temperature, change in mental status, lethargy, change in oxygen status, or cough; 9 (11.0%) did not have fever, cough, or shortness of breath during their clinical course. Those with change in oxygen status had an increased relative risk (RR) of 30-day mortality [51.1% vs 29.7%, RR 1.7, 95% confidence interval (CI) 1.0-3.0]. RR of hospitalization was higher for residents with underlying hepatic disease (1.6, 95% CI 1.1-2.2) or obesity (1.5, 95% CI 1.1-2.1); RR of death was not statistically significant. CONCLUSIONS AND IMPLICATIONS: Our findings reinforce the critical role that monitoring of signs and symptoms can have in identifying COVID-19 cases early. SNFs should ensure they have a systematic approach for responding to abnormal vital signs and oxygen saturation and consider ensuring common signs and symptoms identified in Facility A are among those they monitor.

BACKGROUND: SARS-CoV-2 outbreaks in nursing homes can be large with high case fatality. Identifying asymptomatic individuals early through serial testing is recommended to control COVID-19 in nursing homes, both in response to an outbreak ("outbreak testing" of residents and healthcare personnel) and in facilities without outbreaks ("non-outbreak testing" of healthcare personnel). The effectiveness of outbreak testing and isolation with or without non-outbreak testing was evaluated. METHODS: Using published SARS-CoV-2 transmission parameters, the fraction of SARS-CoV-2 transmissions prevented through serial testing (weekly, every three days, or daily) and isolation of asymptomatic persons compared to symptom-based testing and isolation was evaluated through mathematical modeling using a Reed-Frost model to estimate the percentage of cases prevented (i.e., "effectiveness") through either outbreak testing alone or outbreak plus non-outbreak testing. The potential effect of simultaneous decreases (by 10%) in the effectiveness of isolating infected individuals when instituting testing strategies was also evaluated. RESULTS: Modeling suggests that outbreak testing could prevent 54% (weekly testing with 48-hour test turnaround) to 92% (daily testing with immediate results and 50% relative sensitivity) of SARS-CoV-2 infections. Adding non-outbreak testing could prevent up to an additional 8% of SARS-CoV-2 infections (depending on test frequency and turnaround time). However, added benefits of non-outbreak testing were mostly negated if accompanied by decreases in infection control practice. CONCLUSIONS: When combined with high-quality infection control practices, outbreak testing could be an effective approach to preventing COVID-19 in nursing homes, particularly if optimized through increased test frequency and use of tests with rapid turnaround.