Symptoms, viral loads, and rebound among COVID-19 outpatients treated with nirmatrelvir/ritonavir compared to propensity score matched untreated individuals.

BACKGROUND: Nirmatrelvir/ritonavir (N/R) reduces severe outcomes among patients with COVID-19; however, rebound after treatment has been reported. We compared symptom and viral dynamics in community-based individuals with COVID-19 who completed N/R and similar untreated individuals. METHODS: We identified symptomatic participants who tested SARS-CoV-2 positive and were N/R eligible from a COVID-19 household transmission study: index cases from ambulatory settings and their households were enrolled, collecting daily symptoms, medication use, and respiratory specimens for quantitative PCR for 10 days, March 2022-May 2023. Participants who completed N/R (treated) were propensity score matched to untreated participants. We compared symptom rebound, viral load (VL) rebound, average daily symptoms, and average daily VL by treatment status measured after N/R completion or, if untreated, seven days after symptom onset. RESULTS: Treated (n=130) and untreated participants (n=241) had similar baseline characteristics. After treatment completion, treated participants had greater occurrence of symptom rebound (32% vs 20%; p=0.009) and VL rebound (27% vs 7%; p<0.001). Average daily symptoms were lower among treated participants compared to untreated participants without symptom rebound (1.0 vs 1.6; p<0.01), but not statistically lower with symptom rebound (3.0 vs 3.4; p=0.5). Treated participants had lower average daily VLs without VL rebound (0.9 vs 2.6; p<0.01), but not statistically lower with VL rebound (4.8 vs 5.1; p=0.7). CONCLUSIONS: Individuals who completed N/R experienced fewer symptoms and lower VL but were more likely to have rebound compared to untreated individuals. Providers should still prescribe N/R, when indicated, and communicate possible increased rebound risk to patients.

Pulmonary Illness Related to E-Cigarette Use in Illinois and Wisconsin - Final Report.

BACKGROUND: E-cigarettes are battery-operated devices that heat a liquid and deliver an aerosolized product to the user. Pulmonary illnesses related to e-cigarette use have been reported, but no large series has been described. In July 2019, the Wisconsin Department of Health Services and the Illinois Department of Public Health received reports of lung injury associated with the use of e-cigarettes (also called vaping) and launched a coordinated public health investigation. METHODS: We defined case patients as persons who reported use of e-cigarette devices and related products in the 90 days before symptom onset and had pulmonary infiltrates on imaging and whose illnesses were not attributed to other causes. Medical record abstraction and case patient interviews were conducted with the use of standardized tools. RESULTS: There were 98 case patients, 79% of whom were male; the median age of the patients was 21 years. The majority of patients presented with respiratory symptoms (97%), gastrointestinal symptoms (77%), and constitutional symptoms (100%). All case patients had bilateral infiltrates on chest imaging. A total of 95% of the patients were hospitalized, 26% underwent intubation and mechanical ventilation, and two deaths were reported. A total of 89% of the patients reported having used tetrahydrocannabinol products in e-cigarette devices, although a wide variety of products and devices was reported. Syndromic surveillance data from Illinois showed that the mean monthly rate of visits related to severe respiratory illness in June through August of 2019 was twice the rate that was observed in the same months in 2018. CONCLUSIONS: Case patients presented with similar clinical characteristics. Although the definitive substance or substances contributing to injury have not been determined, this initial cluster of illnesses represents an emerging clinical syndrome or syndromes. Additional work is needed to characterize the pathophysiology and to identify the definitive causes.

Hospitalizations and Deaths Associated with EVALI.

BACKGROUND: As of January 7, 2020, a total of 2558 hospitalized patients with nonfatal cases and 60 patients with fatal cases of e-cigarette, or vaping, product use-associated lung injury (EVALI) had been reported to the Centers for Disease Control and Prevention (CDC). METHODS: In a national study, we compared the characteristics of patients with fatal cases of EVALI with those of patients with nonfatal cases to improve the ability of clinicians to identify patients at increased risk for death from the condition. Health departments reported cases of EVALI to the CDC and included, when available, data from medical-record abstractions and patient interviews. Analyses included all the patients with fatal or nonfatal cases of EVALI that were reported to the CDC as of January 7, 2020. We also present three case reports of patients who died from EVALI to illustrate the clinical characteristics common among such patients. RESULTS: Most of the patients with fatal or nonfatal cases of EVALI were male (32 of 60 [53%] and 1666 of 2498 [67%], respectively). The proportion of patients with fatal or nonfatal cases was higher among those who were non-Hispanic white (39 of 49 [80%] and 1104 of 1818 [61%], respectively) than among those in other race or ethnic groups. The proportion of patients with fatal cases was higher among those 35 years of age or older (44 of 60 [73%]) than among those younger than 35 years, but the proportion with nonfatal cases was lower among those 35 years of age or older (551 of 2514 [22%]). Among the patients who had an available medical history, a higher proportion of those with fatal cases than those with nonfatal cases had a history of asthma (13 of 57 [23%] vs. 102 of 1297 [8%]), cardiac disease (26 of 55 [47%] vs. 115 of 1169 [10%]), or a mental health condition (32 of 49 [65%] vs. 575 of 1398 [41%]). A total of 26 of 50 patients (52%) with fatal cases had obesity. Half the patients with fatal cases (25 of 54 [46%]) were seen in an outpatient setting before hospitalization or death. CONCLUSIONS: Chronic conditions, including cardiac and respiratory diseases and mental health conditions, were common among hospitalized patients with EVALI.

Relationship of SARS-CoV-2 Antigen and Reverse Transcription PCR Positivity for Viral Cultures.

We assessed the relationship between antigen and reverse transcription PCR (RT-PCR) test positivity and successful virus isolation. We found that antigen test results were more predictive of virus recovery than RT-PCR results. However, virus was isolated from some antigen-negative and RT-PCR‒positive paired specimens, providing support for the Centers for Disease Control and Prevention antigen testing algorithm.

Changes in Opioid Dispensing by Medical Specialties After the Release of the 2016 CDC Guideline for Prescribing Opioids for Chronic Pain.

OBJECTIVE: To identify changes in opioid prescribing across a diverse array of medical specialties after the release of the 2016 CDC Guideline for Prescribing Opioids for Chronic Pain. DESIGN: Interrupted time-series analysis of data from a commercial prescribing database. SUBJECTS: De-identified recipients of opioid prescriptions dispensed at U.S. retail pharmacies between 2015 and 2019. METHODS: Opioid dispensing data were obtained from the IQVIA Longitudinal Prescription (LRx) database, representing more than 800 million opioid prescriptions. Monthly dispensing rates, dosage in morphine milligram equivalents (MME), and mean prescription duration were calculated across 29 medical specialties. Changes in dispensing after the release of the 2016 CDC Guideline were assessed through interrupted time-series analysis. RESULTS: Declining trends in opioid dispensing accelerated in 24 of 29 specialty groups after the release of the CDC Guideline (P < 0.05 for 15 groups). Decreases were greatest among family medicine clinicians, where declines accelerated by 4.4 prescriptions per month per 100,000 persons (P = 0.005), and surgeons, where declines accelerated by 3.6 prescriptions per month per 100,000 (P = 0.003). CONCLUSIONS: These results illustrate that clinicians likely to provide primary care exhibited the greatest decreases in opioid dispensing. However, specialties outside the scope of the CDC Guideline (e.g., surgery) also exhibited accelerated decreases in prescribing. These declines illustrate that specialties beyond primary care could have interest in evaluating opioid prescribing practices, supporting the importance of specialty-specific guidance that balances the individualized risks and benefits of opioids and the role of non-opioid treatments.

Quantitative comparison of SARS-CoV-2 nucleic acid amplification test and antigen testing algorithms: a decision analysis simulation model.

BACKGROUND: Antigen tests for SARS-CoV-2 offer advantages over nucleic acid amplification tests (NAATs, such as RT-PCR), including lower cost and rapid return of results, but show reduced sensitivity. Public health organizations recommend different strategies for utilizing NAATs and antigen tests. We sought to create a framework for the quantitative comparison of these recommended strategies based on their expected performance. METHODS: We utilized a decision analysis approach to simulate the expected outcomes of six testing algorithms analogous to strategies recommended by public health organizations. Each algorithm was simulated 50,000 times in a population of 100,000 persons seeking testing. Primary outcomes were number of missed cases, number of false-positive diagnoses, and total test volumes. Outcome medians and 95% uncertainty ranges (URs) were reported. RESULTS: Algorithms that use NAATs to confirm all negative antigen results minimized missed cases but required high NAAT capacity: 92,200 (95% UR: 91,200-93,200) tests (in addition to 100,000 antigen tests) at 10% prevalence. Selective use of NAATs to confirm antigen results when discordant with symptom status (e.g., symptomatic persons with negative antigen results) resulted in the most efficient use of NAATs, with 25 NAATs (95% UR: 13-57) needed to detect one additional case compared to exclusive use of antigen tests. CONCLUSIONS: No single SARS-CoV-2 testing algorithm is likely to be optimal across settings with different levels of prevalence and for all programmatic priorities. This analysis provides a framework for selecting setting-specific strategies to achieve acceptable balances and trade-offs between programmatic priorities and resource constraints.

Shedding of Culturable Virus, Seroconversion, and 6-Month Follow-up Antibody Responses in the First 14 Confirmed Cases of Coronavirus Disease 2019 in the United States.

We aimed to characterize presence of culturable virus in clinical specimens during acute illness, and antibody kinetics up to 6 months after symptom onset, among 14 early patients with coronavirus disease 2019 in the United States. We isolated viable severe acute respiratory syndrome coronavirus 2 from real-time reverse-transcription polymerase chain reaction-positive respiratory specimens collected during days 0-8 after onset, but not after. All 13 patients with 2 or more serum specimens developed anti-spike antibodies; 12 developed detectable neutralizing antibodies. We did not isolate virus after detection of neutralizing antibodies. Eight participants provided serum at 6 months after onset; all retained detectable anti-spike immunoglobulin G, and half had detectable neutralizing antibodies. Two participants reported not feeling fully recovered at 6 months.

Epidemiological Correlates of Polymerase Chain Reaction Cycle Threshold Values in the Detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

BACKGROUND: Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has principally been performed through the use of real-time reverse-transcription polymerase chain reaction testing. Results of such tests can be reported as cycle threshold (Ct) values, which may provide semi-quantitative or indirect measurements of viral load. Previous reports have examined temporal trends in Ct values over the course of a SARS-CoV-2 infection. METHODS: Using testing data collected during a prospective household transmission investigation of outpatient and mild coronavirus disease 2019 cases, we examined the relationships between Ct values of the viral RNA N1 target and demographic, clinical, and epidemiological characteristics collected through participant interviews and daily symptom diaries. RESULTS: We found that Ct values are lowest (corresponding to a higher viral RNA concentration) soon after symptom onset and are significantly correlated with the time elapsed since onset (P < .001); within 7 days after symptom onset, the median Ct value was 26.5, compared with a median Ct value of 35.0 occurring 21 days after onset. Ct values were significantly lower among participants under 18 years of age (P = .01) and those reporting upper respiratory symptoms at the time of sample collection (P = .001), and were higher among participants reporting no symptoms (P = .05). CONCLUSIONS: These results emphasize the importance of early testing for SARS-CoV-2 among individuals with symptoms of respiratory illness, and allow cases to be identified and isolated when their viral shedding may be highest.

Performance of Repeat BinaxNOW Severe Acute Respiratory Syndrome Coronavirus 2 Antigen Testing in a Community Setting, Wisconsin, November 2020-December 2020.

Repeating the BinaxNOW antigen test for severe acute respiratory syndrome coronavirus 2 using 2 groups of readers within 30 minutes resulted in high concordance (98.9%) in 2110 encounters. Same-day repeat antigen testing did not significantly improve test sensitivity (77.2% to 81.4%) while specificity remained high (99.6%).

Outbreak of SARS-CoV-2 B.1.617.2 (Delta) Variant Infections Among Incarcerated Persons in a Federal Prison - Texas, July-August 2021.

Incarcerated populations have experienced disproportionately higher rates of COVID-19-related illness and death compared with the general U.S. population, due in part to congregate living environments that can facilitate rapid transmission of SARS-CoV-2, the virus that causes COVID-19, and the high prevalence of underlying medical conditions associated with severe COVID-19 (1,2). The SARS-CoV-2 B.1.617.2 (Delta) variant has caused outbreaks among vaccinated and unvaccinated persons in congregate settings and large public gatherings (3,4). During July 2021, a COVID-19 outbreak involving the Delta variant was identified in a federal prison in Texas, infecting 172 of 233 (74%) incarcerated persons in two housing units. The Federal Bureau of Prisons (BOP) partnered with CDC to investigate. CDC analyzed data on infection status, symptom onset date, hospitalizations, and deaths among incarcerated persons. The attack rate was higher among unvaccinated versus fully vaccinated persons (39 of 42, 93% versus 129 of 185, 70%; p = 0.002).† Four persons were hospitalized, three of whom were unvaccinated, and one person died, who was unvaccinated. Among a subset of 70 persons consenting to an embedded serial swabbing protocol, the median interval between symptom onset and last positive reverse transcription-polymerase chain reaction (RT-PCR) test result in fully vaccinated versus unvaccinated persons was similar (9 versus 11 days, p = 0.37). One or more specimens were culture-positive from five of 12 (42%) unvaccinated and 14 of 37 (38%) fully vaccinated persons for whom viral culture was attempted. In settings where physical distancing is challenging, including correctional and detention facilities, vaccination and implementation of multicomponent prevention strategies (e.g., testing, medical isolation, quarantine, and masking) are critical to limiting SARS-CoV-2 transmission (5).

Update: Product, Substance-Use, and Demographic Characteristics of Hospitalized Patients in a Nationwide Outbreak of E-cigarette, or Vaping, Product Use-Associated Lung Injury - United States, August 2019-January 2020.

CDC, the Food and Drug Administration (FDA), state and local health departments, and public health and clinical stakeholders continue to investigate a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) (1). EVALI patients in Illinois, Utah, and Wisconsin acquired tetrahydrocannabinol (THC)-containing products primarily from informal sources (2,3). This report updates demographic characteristics and self-reported sources of THC- and nicotine-containing e-cigarette, or vaping, products derived from EVALI patient data reported to CDC by state health departments. As of January 7, 2020, among 1,979 (76%) patients with available data on substance use, a total of 1,620 (82%) reported using any THC-containing products, including 665 (34%) who reported exclusive THC-containing product use. Use of any nicotine-containing products was reported by 1,128 (57%) patients, including 264 (13%) who reported exclusive nicotine-containing product use. Among 809 (50%) patients reporting data on the source of THC-containing products, 131 (16%) reported acquiring their products from only commercial sources (i.e., recreational dispensaries, medical dispensaries, or both; vape or smoke shops; stores; and pop-up shops), 627 (78%) from only informal sources (i.e., friends, family, in-person or online dealers, or other sources), and 51 (6%) from both types of sources. Among 613 (54%) EVALI patients reporting nicotine-containing product use with available data on product source, 421 (69%) reported acquiring their products from only commercial sources, 103 (17%) from only informal sources, and 89 (15%) from both types of sources. Adolescents aged 13-17 years were more likely to acquire both THC- and nicotine-containing products from informal sources than were persons in older age groups. The high prevalence of acquisition of THC-containing products from informal sources by EVALI patients reinforces CDC's recommendation to not use e-cigarette, or vaping, products that contain THC, especially those acquired from informal sources. Although acquisition of nicotine-containing products through informal sources was not common overall, it was common among persons aged <18 years. While the investigation continues, CDC recommends that the best way for persons to ensure that they are not at risk is to consider refraining from the use of all e-cigarette, or vaping, products.

Recent Increase in COVID-19 Cases Reported Among Adults Aged 18-22 Years - United States, May 31-September 5, 2020.

Although children and young adults are reportedly at lower risk for severe disease and death from infection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), than are persons in other age groups (1), younger persons can experience infection and subsequently transmit infection to those at higher risk for severe illness (2-4). Although at lower risk for severe disease, some young adults experience serious illness, and asymptomatic or mild cases can result in sequelae such as myocardial inflammation (5). In the United States, approximately 45% of persons aged 18-22 years were enrolled in colleges and universities in 2019 (6). As these institutions reopen, opportunities for infection increase; therefore, mitigation efforts and monitoring reports of COVID-19 cases among young adults are important. During August 2-September 5, weekly incidence of COVID-19 among persons aged 18-22 years rose by 55.1% nationally; across U.S. Census regions,* increases were greatest in the Northeast, where incidence increased 144.0%, and Midwest, where incidence increased 123.4%. During the same period, changes in testing volume for SARS-CoV-2 in this age group ranged from a 6.2% decline in the West to a 170.6% increase in the Northeast. In addition, the proportion of cases in this age group among non-Hispanic White (White) persons increased from 33.8% to 77.3% during May 31-September 5. Mitigation and preventive measures targeted to young adults can likely reduce SARS-CoV-2 transmission among their contacts and communities. As colleges and universities resume operations, taking steps to prevent the spread of COVID-19 among young adults is critical (7).

Race, Ethnicity, and Age Trends in Persons Who Died from COVID-19 - United States, May-August 2020.

During February 12-October 15, 2020, the coronavirus disease 2019 (COVID-19) pandemic resulted in approximately 7,900,000 aggregated reported cases and approximately 216,000 deaths in the United States.* Among COVID-19-associated deaths reported to national case surveillance during February 12-May 18, persons aged ≥65 years and members of racial and ethnic minority groups were disproportionately represented (1). This report describes demographic and geographic trends in COVID-19-associated deaths reported to the National Vital Statistics System† (NVSS) during May 1-August 31, 2020, by 50 states and the District of Columbia. During this period, 114,411 COVID-19-associated deaths were reported. Overall, 78.2% of decedents were aged ≥65 years, and 53.3% were male; 51.3% were non-Hispanic White (White), 24.2% were Hispanic or Latino (Hispanic), and 18.7% were non-Hispanic Black (Black). The number of COVID-19-associated deaths decreased from 37,940 in May to 17,718 in June; subsequently, counts increased to 30,401 in July and declined to 28,352 in August. From May to August, the percentage distribution of COVID-19-associated deaths by U.S. Census region increased from 23.4% to 62.7% in the South and from 10.6% to 21.4% in the West. Over the same period, the percentage distribution of decedents who were Hispanic increased from 16.3% to 26.4%. COVID-19 remains a major public health threat regardless of age or race and ethnicity. Deaths continued to occur disproportionately among older persons and certain racial and ethnic minorities, particularly among Hispanic persons. These results can inform public health messaging and mitigation efforts focused on prevention and early detection of infection among disproportionately affected groups.

Update: Characteristics of a Nationwide Outbreak of E-cigarette, or Vaping, Product Use-Associated Lung Injury - United States, August 2019-January 2020.

Since August 2019, CDC, the Food and Drug Administration (FDA), state and local health departments, and public health and clinical stakeholders have been investigating a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) (1). This report updates patient demographic characteristics, self-reported substance use, and hospitalization dates for EVALI patients reported to CDC by states, as well as the distribution of emergency department (ED) visits related to e-cigarette, or vaping, products analyzed through the National Syndromic Surveillance Program (NSSP). As of January 14, 2020, a total of 2,668 hospitalized EVALI cases had been reported to CDC. Median patient age was 24 years, and 66% were male. Overall, 82% of EVALI patients reported using any tetrahydrocannabinol (THC)-containing e-cigarette, or vaping, product (including 33% with exclusive THC-containing product use), and 57% of EVALI patients reported using any nicotine-containing product (including 14% with exclusive nicotine-containing product use). Syndromic surveillance indicates that ED visits related to e-cigarette, or vaping, products continue to decline after sharply increasing in August 2019 and peaking in September 2019. Clinicians and public health practitioners should remain vigilant for new EVALI cases. CDC recommends that persons not use THC-containing e-cigarette, or vaping, products, especially those acquired from informal sources such as friends, family members, or from in-person or online dealers. Vitamin E acetate is strongly linked to the EVALI outbreak and should not be added to any e-cigarette, or vaping, products (2). However, evidence is not sufficient to rule out the contribution of other chemicals of concern, including chemicals in either THC- or non-THC-containing products, in some reported EVALI cases.

Severe Pulmonary Disease Associated with Electronic-Cigarette-Product Use - Interim Guidance.

On September 6, 2019, this report was posted as an MMWR Early Release on the MMWR website (https://www.cdc.gov/mmwr). As of August 27, 2019, 215 possible cases of severe pulmonary disease associated with the use of electronic cigarette (e-cigarette) products (e.g., devices, liquids, refill pods, and cartridges) had been reported to CDC by 25 state health departments. E-cigarettes are devices that produce an aerosol by heating a liquid containing various chemicals, including nicotine, flavorings, and other additives (e.g., propellants, solvents, and oils). Users inhale the aerosol, including any additives, into their lungs. Aerosols produced by e-cigarettes can contain harmful or potentially harmful substances, including heavy metals such as lead, volatile organic compounds, ultrafine particles, cancer-causing chemicals, or other agents such as chemicals used for cleaning the device (1). E-cigarettes also can be used to deliver tetrahydrocannabinol (THC), the principal psychoactive component of cannabis, or other drugs; for example, "dabbing" involves superheating substances that contain high concentrations of THC and other plant compounds (e.g., cannabidiol) with the intent of inhaling the aerosol. E-cigarette users could potentially add other substances to the devices. This report summarizes available information and provides interim case definitions and guidance for reporting possible cases of severe pulmonary disease. The guidance in this report reflects data available as of September 6, 2019; guidance will be updated as additional information becomes available.

Linking Individual Natural History to Population Outcomes in Tuberculosis.

Background: Substantial individual heterogeneity exists in the clinical manifestations and duration of active tuberculosis. We sought to link the individual-level characteristics of tuberculosis disease to observed population-level outcomes. Methods: We developed an individual-based, stochastic model of tuberculosis disease in a hypothetical cohort of patients with smear-positive tuberculosis. We conceptualized the disease process as consisting of 2 states-progression and recovery-including transitions between the 2. We then used a Bayesian process to calibrate the model to clinical data from the prechemotherapy era, thus identifying the rates of progression and recovery (and probabilities of transition) consistent with observed population-level clinical outcomes. Results: Observed outcomes are consistent with slow rates of disease progression (median doubling time: 84 days, 95% uncertainty range 62-104) and a low, but nonzero, probability of transition from disease progression to recovery (median 16% per year, 95% uncertainty range 11%-21%). Other individual-level dynamics were less influential in determining observed outcomes. Conclusions: This simplified model identifies individual-level dynamics-including a long doubling time and low probability of immune recovery-that recapitulate population-level clinical outcomes of untreated tuberculosis patients. This framework may facilitate better understanding of the population-level impact of interventions acting at the individual host level.

Fitness Costs of Drug Resistance Mutations in Multidrug-Resistant Mycobacterium tuberculosis: A Household-Based Case-Control Study.

BACKGROUND: The projected long-term prevalence of multidrug-resistant (MDR) tuberculosis depends upon the relative fitness of MDR Mycobacterium tuberculosis strains, compared with non-MDR strains. While many experimental models have tested the in vitro or in vivo fitness costs of various drug resistance mutations, fewer epidemiologic studies have attempted to validate these experimental findings. METHODS: We performed a case-control study comparing drug resistance-associated mutations from MDR M. tuberculosis strains causing multiple cases in a household to matched MDR strains without evidence of secondary household cases. RESULTS: Eighty-eight multiple-case and 88 single-case household MDR strains were analyzed for 10 specific drug resistance-associated polymorphisms previously associated with fitness effects. We found that the isoniazid-resistant katG Ser315Thr mutation occurred more than twice as frequently in multiple-case households than in single-case households (odds ratio [OR], 2.39; 95% confidence interval [CI], 1.21-4.70), corroborating previous experimental findings. However, strains carrying both the katG Ser315Thr mutation and the rpsL Lys43Arg mutation were less likely to be found in multiple-case households (OR, 0.09; 95% CI, .01-.73), suggesting a negative epistatic interaction which contrasts previous findings. CONCLUSIONS: The case-control design presents a useful approach for assessing in vivo fitness effects of drug resistance mutations.

Tracking rural health facility financial data in resource-limited settings: a case study from Rwanda.

Chunling Lu and colleagues describe a project for tracking health center financial data in two rural districts of Rwanda, which could be adapted for other low- or middle-income countries. Please see later in the article for the Editors' Summary.

US-Mexico binational COVID-19 cases in southern California border counties, California, February-June 2020.

Background: COVID-19 has had a significant public health impact on both the United States and Mexico. Cross-border mobility between southern California and Mexico raises questions of transmission trends between these jurisdictions. The objective of this project was to describe binational cases amongst California US-Mexico border county COVID-19 cases and compare incidence trends to cross-border Mexico jurisdictions. Methods: Interview data from persons with confirmed SARS-CoV-2 infections in San Diego County, CA and Imperial County, CA from February to June 2020 were reviewed for binational cases; demographics and connection to COVID-19 outbreaks were assessed. Graphs of COVID-19 incidence in San Diego County and Imperial County were compared to incidence graphs in cross-border Mexico jurisdictions of Tijuana and Mexicali. Results: Persons with COVID-19 and a binational case were older, more likely to be Hispanic, and reside in a border ZIP code than those without. Binational cases were a small proportion and tracked with overall cases during the study period. Conclusions: Binational cases had different trends than non-binational cases of SARS-CoV-2 in San Diego and Imperial counties from February to June 2020. Findings could inform SARS-CoV-2 mitigation strategies specific to the US-Mexico land border, particularly recommendations regarding cross-border land travel.

Cost-effectiveness of point-of-care versus centralised, laboratory-based nucleic acid testing for diagnosis of HIV in infants: a systematic review of modelling studies.

BACKGROUND: Point-of-care (POC) nucleic acid testing for diagnosis of HIV in infants facilitates earlier initiation of antiretroviral therapy (ART) than with centralised (standard-of-care, SOC) testing, but can be more expensive. We evaluated cost-effectiveness data from mathematical models comparing POC with SOC to provide global policy guidance. METHODS: In this systematic review of modelling studies, we searched PubMed, MEDLINE, Embase, the National Health Service Economic Evaluation Database, Econlit, and conference abstracts, combining terms for "HIV" + "infant"/"early infant diagnosis" + "point-of-care" + "cost-effectiveness" + "mathematical models", without restrictions from database inception to July 15, 2022. We selected reports of mathematical cost-effectiveness models comparing POC with SOC for HIV diagnosis in infants younger than 18 months. Titles and abstracts were independently reviewed, with full-text review for qualifying articles. We extracted data on health and economic outcomes and incremental cost-effectiveness ratios (ICERs) for narrative synthesis. The primary outcomes of interest were ICERs (comparing POC with SOC) for ART initiation and survival of children living with HIV. FINDINGS: Our search identified 75 records through database search. 13 duplicates were excluded, leaving 62 non-duplicate articles. 57 records were excluded and five were reviewed in full text. One article was excluded as it was not a modelling study, and four qualifying studies were included in the review. These four reports were from two mathematical models from two independent modelling groups. Two reports used the Johns Hopkins model to compare POC with SOC for repeat early infant diagnosis testing in the first 6 months in sub-Saharan Africa (first report, simulation of 25 000 children) and Zambia (second report, simulation of 7500 children). In the base scenario, POC versus SOC increased probability of ART initiation within 60 days of testing from 19% to 82% (ICER per additional ART initiation range US$430-1097; 9-month cost horizon) in the first report; and from 28% to 81% in the second ($23-1609, 5-year cost horizon). Two reports compared POC with SOC for testing at 6 weeks in Zimbabwe using the Cost-Effectiveness of Preventing AIDS Complications-Paediatric model (simulation of 30 million children; lifetime horizon). POC increased life expectancy and was considered cost-effective compared with SOC (ICER $711-850 per year of life saved in HIV-exposed children). Results were robust throughout sensitivity and scenario analyses. In most scenarios, platform cost-sharing (co-use with other programmes) resulted in POC being cost-saving compared with SOC. INTERPRETATION: Four reports from two different models suggest that POC is a cost-effective and potentially cost-saving strategy for upscaling of early infant testing compared with SOC. FUNDING: Bill & Melinda Gates Foundation, Unitaid, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, WHO, and Massachusetts General Hospital Research Scholars.