Epidemiology of the 2022 Mpox Outbreak in the US Veterans Health Administration.

BACKGROUND: In May 2022, mpox cases were reported in nonendemic countries, including the United States. We examined mpox infections in the Veterans Health Administration (VHA). METHODS: Mpox diagnostic and whole genome sequencing (WGS) results, demographics, risk factors, hospitalizations, exposures, deaths, and pharmacy and immunization data were obtained from VHA data sources (23 May 2022-31 May 2023). RESULTS: Of 1144 Veterans tested, 251 (21.9%) were presumptive positive for nonvariola orthopoxvirus (NVO) or confirmed positive for NVO and Monkeypox virus (MPXV). Incidence rate was 7.5 per 100 000 Veterans in care, with the highest rate observed in Veterans aged 25-34 years (13.83 cases per 100 000). Higher odds of NVO or NVO/MPXV positivity was associated with male sex; non-Hispanic Black race/ethnicity; syphilis or human immunodeficiency virus (HIV) positivity; or genital/rectal sample site, whereas older age and vaccination with JYNNEOS or vaccinia (smallpox) had lower odds. Among 209 with confirmatory testing, 90.4% reported intimate contact and/or an epidemiological link, 84.5% were men who have sex with men (MSM), 24.2% received tecovirimat, and 8.1% were hospitalized with 1 death. Eighty-six sequenced samples had evaluable WGS results. All were clade IIb, representing 10 different lineages from 20 states and the District of Columbia. CONCLUSIONS: Mpox affected younger, MSM, non-Hispanic Black, and HIV/syphilis-positive men among US Veterans. Viral diversity was noted across geographic regions. At-risk Veterans would benefit from vaccination and risk reduction strategies for mpox and other sexually transmitted infections.

Effect of Neutralizing Monoclonal Antibody Treatment on Early Trajectories of Virologic and Immunologic Biomarkers in Patients Hospitalized With COVID-19.

BACKGROUND: Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood. METHODS: Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo. Longitudinal differences between treatment and placebo groups in levels of plasma nucleocapsid antigen (N-Ag), anti-nucleocapsid antibody, C-reactive protein, interleukin-6, and D-dimer at enrollment, day 1, 3, and 5 were estimated using linear mixed models. A 7-point pulmonary ordinal scale assessed at day 5 was compared using proportional odds models. RESULTS: Analysis included 2149 participants enrolled between August 2020 and September 2021. Treatment resulted in 20% lower levels of plasma N-Ag compared with placebo (95% confidence interval, 12%-27%; P < .001), and a steeper rate of decline through the first 5 days (P < .001). The treatment difference did not vary between subgroups, and no difference was observed in trajectories of other biomarkers or the day 5 pulmonary ordinal scale. CONCLUSIONS: Our study suggests that nmAb has an antiviral effect assessed by plasma N-Ag among hospitalized patients with COVID-19, with no blunting of the endogenous anti-nucleocapsid antibody response. No effect on systemic inflammation or day 5 clinical status was observed. CLINICAL TRIALS REGISTRATION: NCT04501978.

Viral and Host Factors Are Associated With Mortality in Hospitalized Patients With COVID-19.

BACKGROUND: Persistent mortality in adults hospitalized due to acute COVID-19 justifies pursuit of disease mechanisms and potential therapies. The aim was to evaluate which virus and host response factors were associated with mortality risk among participants in Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3) trials. METHODS: A secondary analysis of 2625 adults hospitalized for acute SARS-CoV-2 infection randomized to 1 of 5 antiviral products or matched placebo in 114 centers on 4 continents. Uniform, site-level collection of participant baseline clinical variables was performed. Research laboratories assayed baseline upper respiratory swabs for SARS-CoV-2 viral RNA and plasma for anti-SARS-CoV-2 antibodies, SARS-CoV-2 nucleocapsid antigen (viral Ag), and interleukin-6 (IL-6). Associations between factors and time to mortality by 90 days were assessed using univariate and multivariable Cox proportional hazards models. RESULTS: Viral Ag ≥4500 ng/L (vs <200 ng/L; adjusted hazard ratio [aHR], 2.07; 1.29-3.34), viral RNA (<35 000 copies/mL [aHR, 2.42; 1.09-5.34], ≥35 000 copies/mL [aHR, 2.84; 1.29-6.28], vs below detection), respiratory support (<4 L O2 [aHR, 1.84; 1.06-3.22]; ≥4 L O2 [aHR, 4.41; 2.63-7.39], or noninvasive ventilation/high-flow nasal cannula [aHR, 11.30; 6.46-19.75] vs no oxygen), renal impairment (aHR, 1.77; 1.29-2.42), and IL-6 >5.8 ng/L (aHR, 2.54 [1.74-3.70] vs ≤5.8 ng/L) were significantly associated with mortality risk in final adjusted analyses. Viral Ag, viral RNA, and IL-6 were not measured in real-time. CONCLUSIONS: Baseline virus-specific, clinical, and biological variables are strongly associated with mortality risk within 90 days, revealing potential pathogen and host-response therapeutic targets for acute COVID-19 disease.

Trends in Follow-up Testing Among Patients Positive for Chlamydia and Gonorrhea in the Veterans Health Administration, 2013 to 2019.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) recommends testing patients with chlamydia (CT)/gonorrhea (GC) for other sexually transmitted infections (STIs) and repeating CT/GC testing 3 to 12 months later. We assessed repeat CT/GC testing and testing for HIV/syphilis in accordance with CDC guidelines in the US Veterans Health Administration. METHODS: Molecular laboratory testing for CT/GC during January 1, 2013-December 31, 2020 was retrieved from Veterans Health Administration data sources. Patients were evaluated for syphilis, HIV, and repeat CT/GC testing within 1 year after a positive CT/GC test result. Differences of CT/GC-positive patients associated with receiving recommended testing were assessed using χ2 /Fisher exact tests. RESULTS: A total of 41,630 of 1,005,761 CT (4.1%) and 17,649 of 1,013,198 GC (1.7%) results were positive. Median ages of positive CT/GC patients were 29 and 36 years, respectively. Repeat testing rates for CT/GC within 90 to 119 days were 3.9% and 2.9%, and rates within 90 to 365 days were 32.8% and 34.7%, with 8.6% and 15% being positive again, respectively. Guideline-compatible repeat testing in known HIV-positive patients nearly doubled (75.7% for CT and 67.8% for GC). The CDC-recommended HIV testing was performed for 72.4% and 65.5% CT and GC first positives, respectively, whereas syphilis testing was completed for 66.5% and 60.5% CT and GC, respectively. Compared with 25- to 34-year-old patients with CT or GC, those younger than 25 years had higher odds of guideline-discordant repeat testing but had lower odds of not receiving HIV/syphilis testing. CONCLUSIONS: Nearly two-thirds of patients did not receive recommended repeat testing, and nearly one-third were not tested for HIV/syphilis. Veterans Health Administration providers may benefit from additional education on CDC-recommended sexually transmitted infection guidelines and testing recommendations.

Effectiveness of Messenger RNA-based Vaccines During the Emergence of the Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant.

BACKGROUND: We evaluated the effectiveness of mRNA-based vaccines following emergence of SARS-CoV-2 Omicron variant. METHODS: Recipients of a third dose of BNT162b2 or mRNA-1273 ≥180 days after the primary series were matched to primary-series recipients and unvaccinated persons. Participants were followed from 1 December 2021 to 12 March 2022. Outcomes were documented SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19 death. Effectiveness was calculated from 100-day risks estimated with the Kaplan-Meier estimator. RESULTS: BNT162b2 and mRNA-1273 groups included 221 267 and 187 507 third-dose recipients, respectively, matched to equal numbers of primary-series recipients and unvaccinated persons. Compared with no vaccination, effectiveness of a third dose of BNT162b2 was 47.8% (95% confidence interval [CI], 45.2-50.3), 81.8% (95% CI, 79.2-84.2), and 89.6% (95% CI, 85.0-93.6) against infection, hospitalization, and death, respectively. Effectiveness of a third dose of BNT162b2 compared with the primary series was 30.1% (95% CI, 26.2-33.7), 61.4% (95% CI, 55.0-67.1), and 78.8% (95% CI, 67.9-87.5) against infection, hospitalization, and death, respectively. Effectiveness of a third dose of mRNA-1273 compared with no vaccination was 61.9% (95% CI, 59.4-64.4), 87.9% (95% CI, 85.3-90.2), and 91.4% (95% CI, 86.4-95.6) against infection, hospitalization, and death, respectively. Effectiveness of a third dose of mRNA-1273 compared with the primary series was 37.1% (95% CI, 32.2-41.7), 63.5% (95% CI, 53.7-71.6), and 75.0% (95% CI, 55.4-88.0) against infection, hospitalization, and death, respectively. CONCLUSIONS: BNT162b2 and mRNA-1273 were effective against COVID-19 following emergence of Omicron variant. A third dose provided additional protection over the primary series.

Exposure Sources Among Veterans With Elevated Blood Lead Levels, United States, 2015‒2021.

Objectives. To determine characteristics and sources of exposure in veterans with elevated blood lead levels (BLLs). Methods. We included users of US Veterans Health Administration care aged 18 years or older tested for BLL from October 2015 to September 2021. Prevalence of BLL 10 micrograms per deciliter (µg/dL) or higher and 25 µg/dL or higher was determined within demographic groups. Logistic regression analysis measured association of International Classification of Diseases, Tenth Revision, Clinical Modification‒coded conditions with elevated BLL. Electronic notes were reviewed for exposure sources. Results. Among 1007 unique veterans with BLL 10 µg/dL or higher, prevalence of BLL 10 µg/dL or higher and 25 µg/dL or higher peaked at 4.9 and 1.3 per 100 000 veterans, respectively (fiscal year 2019), and was highest in non-Hispanic White men and those aged 25 to 34 years. Conditions predicted by elevated BLL were attention-deficit/hyperactivity disorder (ADHD) and nausea or vomiting. Firearms represented 70.1% of occupational and 85.9% of nonoccupational exposures. Toxicology consults occurred in 17 of 298 (6%) with BLL 25 µg/dL or higher. Conclusions. Firearms were the largest exposure source among veterans with elevated BLL. Clinicians should be alert for potential conditions (including ADHD and nausea or vomiting in our study) associated with lead exposure. Standardization of care regarding toxicology referral practices is warranted. (Am J Public Health. 2022;112(S7):S670-S678. https://doi.org/10.2105/AJPH.2022.306936).

Public health surveillance in the U.S. Department of Veterans Affairs: evaluation of the Praedico surveillance system.

BACKGROUND: Early threat detection and situational awareness are vital to achieving a comprehensive and accurate view of health-related events for federal, state, and local health agencies. Key to this are public health and syndromic surveillance systems that can analyze large data sets to discover patterns, trends, and correlations of public health significance. In 2020, Department of Veterans Affairs (VA) evaluated its public health surveillance system and identified areas for improvement. METHODS: Using the Centers for Disease Control and Prevention (CDC) Guidelines for Evaluating Public Health Surveillance Systems, we assessed the ability of the Praedico Surveillance System to perform public health surveillance for a variety of health issues and evaluated its performance compared to an enterprise data solution (VA Corporate Data Warehouse), legacy surveillance system (VA ESSENCE) and a national, collaborative syndromic surveillance platform (CDC NSSP BioSense). RESULTS: Review of system attributes found that the system was simple, flexible, and stable. Representativeness, timeliness, sensitivity, and Predictive Value Positive were acceptable but could be further improved. Data quality issues and acceptability present challenges that potentially affect the overall usefulness of the system. CONCLUSIONS: Praedico is a customizable surveillance and data analytics platform built on big data technologies. Functionality is straightforward, with rapid query generation and runtimes. Data can be graphed, mapped, analyzed, and shared with key decision makers and stakeholders. Evaluation findings suggest that future development and system enhancements should focus on addressing Praedico data quality issues and improving user acceptability. Because Praedico is designed to handle big data queries and work with data from a variety of sources, it could be enlisted as a tool for interdepartmental and interagency collaboration and public health data sharing. We suggest that future system evaluations include measurements of value and effectiveness along with additional organizations and functional assessments.

A Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Prediction Model From Standard Laboratory Tests.

BACKGROUND: With the limited availability of testing for the presence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and concerns surrounding the accuracy of existing methods, other means of identifying patients are urgently needed. Previous studies showing a correlation between certain laboratory tests and diagnosis suggest an alternative method based on an ensemble of tests. METHODS: We have trained a machine learning model to analyze the correlation between SARS-CoV-2 test results and 20 routine laboratory tests collected within a 2-day period around the SARS-CoV-2 test date. We used the model to compare SARS-CoV-2 positive and negative patients. RESULTS: In a cohort of 75 991 veteran inpatients and outpatients who tested for SARS-CoV-2 in the months of March through July 2020, 7335 of whom were positive by reverse transcription polymerase chain reaction (RT-PCR) or antigen testing, and who had at least 15 of 20 lab results within the window period, our model predicted the results of the SARS-CoV-2 test with a specificity of 86.8%, a sensitivity of 82.4%, and an overall accuracy of 86.4% (with a 95% confidence interval of [86.0%, 86.9%]). CONCLUSIONS: Although molecular-based and antibody tests remain the reference standard method for confirming a SARS-CoV-2 diagnosis, their clinical sensitivity is not well known. The model described herein may provide a complementary method of determining SARS-CoV-2 infection status, based on a fully independent set of indicators, that can help confirm results from other tests as well as identify positive cases missed by molecular testing.

Incidence, Etiology, and Severity of Acute Gastroenteritis Among Prospectively Enrolled Patients in 4 Veterans Affairs Hospitals and Outpatient Centers, 2016-2018.

BACKGROUND: Acute gastroenteritis (AGE) burden, etiology, and severity in adults is not well characterized. We implemented a multisite AGE surveillance platform in 4 Veterans Affairs Medical Centers (Atlanta, Georgia; Bronx, New York; Houston, Texas; and Los Angeles, California), collectively serving >320 000 patients annually. METHODS: From 1 July 2016 to 30 June 2018, we actively identified inpatient AGE case patients and non-AGE inpatient controls through prospective screening of admitted patients and passively identified outpatients with AGE through stool samples submitted for clinical diagnostics. We abstracted medical charts and tested stool samples for 22 pathogens by means of multiplex gastrointestinal polymerase chain reaction panel followed by genotyping of norovirus- and rotavirus-positive samples. We determined pathogen-specific prevalence, incidence, and modified Vesikari severity scores. RESULTS: We enrolled 724 inpatients with AGE, 394 non-AGE inpatient controls, and 506 outpatients with AGE. Clostridioides difficile and norovirus were most frequently detected among inpatients (for AGE case patients vs controls: C. difficile, 18.8% vs 8.4%; norovirus, 5.1% vs 1.5%; P < .01 for both) and outpatients (norovirus, 10.7%; C. difficile, 10.5%). The incidence per 100 000 population was highest among outpatients (AGE, 2715; C. difficile, 285; norovirus, 291) and inpatients ≥65 years old (AGE, 459; C. difficile, 91; norovirus, 26). Clinical severity scores were highest for inpatient norovirus, rotavirus, and Shigella/enteroinvasive Escherichia coli cases. Overall, 12% of inpatients with AGE had intensive care unit stays, and 2% died; 3 deaths were associated with C. difficile and 1 with norovirus. C. difficile and norovirus were detected year-round with a fall/winter predominance. CONCLUSIONS: C. difficile and norovirus were leading AGE pathogens in outpatient and hospitalized US veterans, resulting in severe disease. Clinicians should remain vigilant for bacterial and viral causes of AGE year-round.

Effectiveness of COVID-19 mRNA Vaccines Against COVID-19-Associated Hospitalization - Five Veterans Affairs Medical Centers, United States, February 1-August 6, 2021.

COVID-19 mRNA vaccines (Pfizer-BioNTech and Moderna) have been shown to be highly protective against COVID-19-associated hospitalizations (1-3). Data are limited on the level of protection against hospitalization among disproportionately affected populations in the United States, particularly during periods in which the B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, predominates (2). U.S. veterans are older, more racially diverse, and have higher prevalences of underlying medical conditions than persons in the general U.S. population (2,4). CDC assessed the effectiveness of mRNA vaccines against COVID-19-associated hospitalization among 1,175 U.S. veterans aged ≥18 years hospitalized at five Veterans Affairs Medical Centers (VAMCs) during February 1-August 6, 2021. Among these hospitalized persons, 1,093 (93.0%) were men, the median age was 68 years, 574 (48.9%) were non-Hispanic Black (Black), 475 were non-Hispanic White (White), and 522 (44.4%) had a Charlson comorbidity index score of ≥3 (5). Overall adjusted vaccine effectiveness against COVID-19-associated hospitalization was 86.8% (95% confidence interval [CI] = 80.4%-91.1%) and was similar before (February 1-June 30) and during (July 1-August 6) SARS-CoV-2 Delta variant predominance (84.1% versus 89.3%, respectively). Vaccine effectiveness was 79.8% (95% CI = 67.7%-87.4%) among adults aged ≥65 years and 95.1% (95% CI = 89.1%-97.8%) among those aged 18-64 years. COVID-19 mRNA vaccines are highly effective in preventing COVID-19-associated hospitalization in this older, racially diverse population of predominately male U.S. veterans. Additional evaluations of vaccine effectiveness among various age groups are warranted. To prevent COVID-19-related hospitalizations, all eligible persons should receive COVID-19 vaccination.

Comparative Effectiveness and Antibody Responses to Moderna and Pfizer-BioNTech COVID-19 Vaccines among Hospitalized Veterans - Five Veterans Affairs Medical Centers, United States, February 1-September 30, 2021.

The mRNA COVID-19 vaccines (Moderna and Pfizer-BioNTech) provide strong protection against severe COVID-19, including hospitalization, for at least several months after receipt of the second dose (1,2). However, studies examining immune responses and differences in protection against COVID-19-associated hospitalization in real-world settings, including by vaccine product, are limited. To understand how vaccine effectiveness (VE) might change with time, CDC and collaborators assessed the comparative effectiveness of Moderna and Pfizer-BioNTech vaccines in preventing COVID-19-associated hospitalization at two periods (14-119 days and ≥120 days) after receipt of the second vaccine dose among 1,896 U.S. veterans at five Veterans Affairs medical centers (VAMCs) during February 1-September 30, 2021. Among 234 U.S. veterans fully vaccinated with an mRNA COVID-19 vaccine and without evidence of current or prior SARS-CoV-2 infection, serum antibody levels (anti-spike immunoglobulin G [IgG] and anti-receptor binding domain [RBD] IgG) to SARS-CoV-2 were also compared. Adjusted VE 14-119 days following second Moderna vaccine dose was 89.6% (95% CI = 80.1%-94.5%) and after the second Pfizer-BioNTech dose was 86.0% (95% CI = 77.6%-91.3%); at ≥120 days VE was 86.1% (95% CI = 77.7%-91.3%) for Moderna and 75.1% (95% CI = 64.6%-82.4%) for Pfizer-BioNTech. Antibody levels were significantly higher among Moderna recipients than Pfizer-BioNTech recipients across all age groups and periods since vaccination; however, antibody levels among recipients of both products declined between 14-119 days and ≥120 days. These findings from a cohort of older, hospitalized veterans with high prevalences of underlying conditions suggest the importance of booster doses to help maintain long-term protection against severe COVID-19.†.

Trends in Incidence of Norovirus-associated Acute Gastroenteritis in 4 Veterans Affairs Medical Center Populations in the United States, 2011-2015.

BACKGROUND: Norovirus is an important cause of epidemic acute gastroenteritis (AGE), yet the burden of endemic disease in adults has not been well documented. We estimated the prevalence and incidence of outpatient and community-acquired inpatient norovirus AGE at 4 Veterans Affairs Medical Centers (VAMC) (Atlanta, Georgia; Bronx, New York; Houston, Texas; and Los Angeles, California) and examined trends over 4 surveillance years. METHODS: From November 2011 to September 2015, stool specimens collected within 7 days of AGE symptom onset for clinician-requested diagnostic testing were tested for norovirus, and positive samples were genotyped. Incidence was calculated by multiplying norovirus prevalence among tested specimens by AGE-coded outpatient encounters and inpatient discharges, and dividing by the number of unique patients served. RESULTS: Of 1603 stool specimens, 6% tested were positive for norovirus; GII.4 viruses (GII.4 New Orleans [17%] and GII.4 Sydney [47%]) were the most common genotypes. Overall prevalence and outpatient and inpatient community-acquired incidence followed a seasonal pattern, with higher median rates during November-April (9.2%, 376/100 000, and 45/100 000, respectively) compared to May-October (3.0%, 131/100 000, and 13/100 000, respectively). An alternate-year pattern was also detected, with highest peak prevalence and outpatient and inpatient community-acquired norovirus incidence rates in the first and third years of surveillance (14%-25%, 349-613/100 000, and 43-46/100 000, respectively). CONCLUSIONS: This multiyear analysis of laboratory-confirmed AGE surveillance from 4 VAMCs demonstrates dynamic intra- and interannual variability in prevalence and incidence of outpatient and inpatient community-acquired norovirus in US Veterans, highlighting the burden of norovirus disease in this adult population.

Validation of Acute Gastroenteritis-related International Classification of Diseases, Clinical Modification Codes in Pediatric and Adult US Populations.

International Classification of Diseases diagnostic codes are used to estimate acute gastroenteritis (AGE) disease burden. We validated AGE-related codes in pediatric and adult populations using 2 multiregional active surveillance platforms. The sensitivity of AGE codes was similar (54% and 58%) in both populations and increased with addition of vomiting-specific codes.

Patterns of COVID-19 testing and mortality by race and ethnicity among United States veterans: A nationwide cohort study.

BACKGROUND: There is growing concern that racial and ethnic minority communities around the world are experiencing a disproportionate burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19). We investigated racial and ethnic disparities in patterns of COVID-19 testing (i.e., who received testing and who tested positive) and subsequent mortality in the largest integrated healthcare system in the United States. METHODS AND FINDINGS: This retrospective cohort study included 5,834,543 individuals receiving care in the US Department of Veterans Affairs; most (91%) were men, 74% were non-Hispanic White (White), 19% were non-Hispanic Black (Black), and 7% were Hispanic. We evaluated associations between race/ethnicity and receipt of COVID-19 testing, a positive test result, and 30-day mortality, with multivariable adjustment for a wide range of demographic and clinical characteristics including comorbid conditions, health behaviors, medication history, site of care, and urban versus rural residence. Between February 8 and July 22, 2020, 254,595 individuals were tested for COVID-19, of whom 16,317 tested positive and 1,057 died. Black individuals were more likely to be tested (rate per 1,000 individuals: 60.0, 95% CI 59.6-60.5) than Hispanic (52.7, 95% CI 52.1-53.4) and White individuals (38.6, 95% CI 38.4-38.7). While individuals from minority backgrounds were more likely to test positive (Black versus White: odds ratio [OR] 1.93, 95% CI 1.85-2.01, p < 0.001; Hispanic versus White: OR 1.84, 95% CI 1.74-1.94, p < 0.001), 30-day mortality did not differ by race/ethnicity (Black versus White: OR 0.97, 95% CI 0.80-1.17, p = 0.74; Hispanic versus White: OR 0.99, 95% CI 0.73-1.34, p = 0.94). The disparity between Black and White individuals in testing positive for COVID-19 was stronger in the Midwest (OR 2.66, 95% CI 2.41-2.95, p < 0.001) than the West (OR 1.24, 95% CI 1.11-1.39, p < 0.001). The disparity in testing positive for COVID-19 between Hispanic and White individuals was consistent across region, calendar time, and outbreak pattern. Study limitations include underrepresentation of women and a lack of detailed information on social determinants of health. CONCLUSIONS: In this nationwide study, we found that Black and Hispanic individuals are experiencing an excess burden of SARS-CoV-2 infection not entirely explained by underlying medical conditions or where they live or receive care. There is an urgent need to proactively tailor strategies to contain and prevent further outbreaks in racial and ethnic minority communities.

Risk for In-Hospital Complications Associated with COVID-19 and Influenza - Veterans Health Administration, United States, October 1, 2018-May 31, 2020.

Coronavirus disease 2019 (COVID-19) is primarily a respiratory illness, although increasing evidence indicates that infection with SARS-CoV-2, the virus that causes COVID-19, can affect multiple organ systems (1). Data that examine all in-hospital complications of COVID-19 and that compare these complications with those associated with other viral respiratory pathogens, such as influenza, are lacking. To assess complications of COVID-19 and influenza, electronic health records (EHRs) from 3,948 hospitalized patients with COVID-19 (March 1-May 31, 2020) and 5,453 hospitalized patients with influenza (October 1, 2018-February 1, 2020) from the national Veterans Health Administration (VHA), the largest integrated health care system in the United States,* were analyzed. Using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes, complications in patients with laboratory-confirmed COVID-19 were compared with those in patients with influenza. Risk ratios were calculated and adjusted for age, sex, race/ethnicity, and underlying medical conditions; proportions of complications were stratified among patients with COVID-19 by race/ethnicity. Patients with COVID-19 had almost 19 times the risk for acute respiratory distress syndrome (ARDS) than did patients with influenza, (adjusted risk ratio [aRR] = 18.60; 95% confidence interval [CI] = 12.40-28.00), and more than twice the risk for myocarditis (2.56; 1.17-5.59), deep vein thrombosis (2.81; 2.04-3.87), pulmonary embolism (2.10; 1.53-2.89), intracranial hemorrhage (2.85; 1.35-6.03), acute hepatitis/liver failure (3.13; 1.92-5.10), bacteremia (2.46; 1.91-3.18), and pressure ulcers (2.65; 2.14-3.27). The risks for exacerbations of asthma (0.27; 0.16-0.44) and chronic obstructive pulmonary disease (COPD) (0.37; 0.32-0.42) were lower among patients with COVID-19 than among those with influenza. The percentage of COVID-19 patients who died while hospitalized (21.0%) was more than five times that of influenza patients (3.8%), and the duration of hospitalization was almost three times longer for COVID-19 patients. Among patients with COVID-19, the risk for respiratory, neurologic, and renal complications, and sepsis was higher among non-Hispanic Black or African American (Black) patients, patients of other races, and Hispanic or Latino (Hispanic) patients compared with those in non-Hispanic White (White) patients, even after adjusting for age and underlying medical conditions. These findings highlight the higher risk for most complications associated with COVID-19 compared with influenza and might aid clinicians and researchers in recognizing, monitoring, and managing the spectrum of COVID-19 manifestations. The higher risk for certain complications among racial and ethnic minority patients provides further evidence that certain racial and ethnic minority groups are disproportionally affected by COVID-19 and that this disparity is not solely accounted for by age and underlying medical conditions.

Carbon monoxide poisoning surveillance in the Veterans Health Administration, 2010-2017.

BACKGROUND: Exposure to carbon monoxide (CO), the odorless, colorless gas resulting from incomplete combustion of hydrocarbons, is preventable. Despite the significant risk of morbidity and mortality associated with CO poisoning, there currently exists no active national CO surveillance system in the United States (U.S.). Our study aims to use electronic health record data to describe the epidemiology of CO poisoning in the Veterans Health Administration healthcare population. METHODS: We identified unique inpatient and outpatient encounters coded with International Classification of Diseases (ICD) codes for CO poisoning and analyzed relevant demographic, laboratory, treatment, and death data from January 2010 through December 2017 for Veterans across all 50 U.S. states and Puerto Rico. Statistical methods used were 95% CI calculations and the two-tailed z test for proportions. RESULTS: We identified 5491 unique patients with CO poisoning, of which 1755 (32%) were confirmed/probable and 3736 (68%) were suspected. Unintentional poisoning was most common (72.9%) overall. Age less than 65 years, residence in Midwest U.S. Census region versus South or West, and winter seasonal trend were characteristics associated with confirmed/probable CO poisoning. Twenty-six deaths (1.5%) occurred within 30 days of confirmed/probable CO poisoning and were primarily caused by cardiovascular events (42%) or anoxic encephalopathy (15%). CONCLUSIONS: Our findings support the use of ICD-coded data for targeted CO poisoning surveillance, however, improvements are needed in ICD coding to reduce the percentage of cases coded with unknown injury intent and/or CO poisoning source. Prevalence of CO poisoning among Veterans is consistent with other U.S. estimates. Since most cases are unintentional, opportunities exist for provider and patient education to reduce risk.

Effect of Interferon-Free Regimens on Disparities in Hepatitis C Treatment of US Veterans.

OBJECTIVES: To determine whether implementation of interferon-free treatment for hepatitis C virus (HCV) reached groups less likely to benefit from earlier therapies, including patients with genotype 1 virus or contraindications to interferon treatment, and groups that faced treatment disparities: African Americans, patients with HIV co-infection, and those with drug use disorder. METHODS: Electronic medical records of the US Veterans Health Administration (VHA) were used to characterize patients with chronic HCV infection and the treatments they received. Initiation of treatment in 206,544 patients with chronic HCV characterized by viral genotype, demographic characteristics, and comorbid medical and mental illness was studied using a competing events Cox regression over 6 years. RESULTS: With the advent of interferon-free regimens, the proportion treated increased from 2.4% in 2010 to 18.1% in 2015, an absolute increase of 15.7%. Patients with genotype 1 virus, poor response to previous treatment, and liver disease had the greatest increase. Large absolute increases in the proportion treated were observed in patients with HIV co-infection (18.6%), alcohol use disorder (11.9%), and drug use disorder (12.6%) and in African American (13.7%) and Hispanic (13.5%) patients, groups that were less likely to receive interferon-containing treatment. The VHA spent $962 million on interferon-free treatments in 2015, 1.5% of its operating budget. CONCLUSIONS: The proportion of patients with HCV treated in VHA increased sevenfold. The VHA was successful in implementing interferon treatment in previously undertreated populations, and this may become the community standard of care.

HIV-1 Protease, Reverse Transcriptase, and Integrase Variation.

UNLABELLED: HIV-1 protease (PR), reverse transcriptase (RT), and integrase (IN) variability presents a challenge to laboratories performing genotypic resistance testing. This challenge will grow with increased sequencing of samples enriched for proviral DNA such as dried blood spots and increased use of next-generation sequencing (NGS) to detect low-abundance HIV-1 variants. We analyzed PR and RT sequences from >100,000 individuals and IN sequences from >10,000 individuals to characterize variation at each amino acid position, identify mutations indicating APOBEC-mediated G-to-A editing, and identify mutations resulting from selective drug pressure. Forty-seven percent of PR, 37% of RT, and 34% of IN positions had one or more amino acid variants with a prevalence of ≥1%. Seventy percent of PR, 60% of RT, and 60% of IN positions had one or more variants with a prevalence of ≥0.1%. Overall 201 PR, 636 RT, and 346 IN variants had a prevalence of ≥0.1%. The median intersubtype prevalence ratios were 2.9-, 2.1-, and 1.9-fold for these PR, RT, and IN variants, respectively. Only 5.0% of PR, 3.7% of RT, and 2.0% of IN variants had a median intersubtype prevalence ratio of ≥10-fold. Variants at lower prevalences were more likely to differ biochemically and to be part of an electrophoretic mixture compared to high-prevalence variants. There were 209 mutations indicative of APOBEC-mediated G-to-A editing and 326 mutations nonpolymorphic treatment selected. Identification of viruses with a high number of APOBEC-associated mutations will facilitate the quality control of dried blood spot sequencing. Identifying sequences with a high proportion of rare mutations will facilitate the quality control of NGS. IMPORTANCE: Most antiretroviral drugs target three HIV-1 proteins: PR, RT, and IN. These proteins are highly variable: many different amino acids can be present at the same position in viruses from different individuals. Some of the amino acid variants cause drug resistance and occur mainly in individuals receiving antiretroviral drugs. Some variants result from a human cellular defense mechanism called APOBEC-mediated hypermutation. Many variants result from naturally occurring mutation. Some variants may represent technical artifacts. We studied PR and RT sequences from >100,000 individuals and IN sequences from >10,000 individuals to quantify variation at each amino acid position in these three HIV-1 proteins. We performed analyses to determine which amino acid variants resulted from antiretroviral drug selection pressure, APOBEC-mediated editing, and naturally occurring variation. Our results provide information essential to clinical, research, and public health laboratories performing genotypic resistance testing by sequencing HIV-1 PR, RT, and IN.

Cost-Effectiveness of HIV Preexposure Prophylaxis for People Who Inject Drugs in the United States.

BACKGROUND: The total population health benefits and costs of HIV preexposure prophylaxis (PrEP) for people who inject drugs (PWID) in the United States are unclear. OBJECTIVE: To evaluate the cost-effectiveness and optimal delivery conditions of PrEP for PWID. DESIGN: Empirically calibrated dynamic compartmental model. DATA SOURCES: Published literature and expert opinion. TARGET POPULATION: Adult U.S. PWID. TIME HORIZON: 20 years and lifetime. INTERVENTION: PrEP alone, PrEP with frequent screening (PrEP+screen), and PrEP+screen with enhanced provision of antiretroviral therapy (ART) for individuals who become infected (PrEP+screen+ART). All scenarios are considered at 25% coverage. OUTCOME MEASURES: Infections averted, deaths averted, change in HIV prevalence, discounted costs (in 2015 U.S. dollars), discounted quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. RESULTS OF BASE-CASE ANALYSIS: PrEP+screen+ART dominates other strategies, averting 26 700 infections and reducing HIV prevalence among PWID by 14% compared with the status quo. Achieving these benefits costs $253 000 per QALY gained. At current drug prices, total expenditures for PrEP+screen+ART could be as high as $44 billion over 20 years. RESULTS OF SENSITIVITY ANALYSIS: Cost-effectiveness of the intervention is linear in the annual cost of PrEP and is dependent on PrEP drug adherence, individual transmission risks, and community HIV prevalence. LIMITATION: Data on risk stratification and achievable PrEP efficacy levels for U.S. PWID are limited. CONCLUSION: PrEP with frequent screening and prompt treatment for those who become infected can reduce HIV burden among PWID and provide health benefits for the entire U.S. population, but, at current drug prices, it remains an expensive intervention both in absolute terms and in cost per QALY gained. PRIMARY FUNDING SOURCE: National Institute on Drug Abuse.