Distinguishing SARS-CoV-2 persistence and reinfection: A retrospective cohort study.

BACKGROUND: SARS-CoV-2 reinfection is poorly understood, partly because few studies have systematically applied genomic analysis to distinguish reinfection from persistent RNA detection related to initial infection. We aimed to evaluate the characteristics of SARS-CoV-2 reinfection and persistent RNA detection using independent genomic, clinical, and laboratory assessments. METHODS: All individuals at a large academic medical center who underwent a SARS-CoV-2 nucleic acid amplification test (NAAT) ≥ 45 days after an initial positive test, with both tests between March 14th and December 30th, 2020, were analyzed for potential reinfection. Inclusion criteria required having ≥2 positive NAATs collected ≥45 days apart with a cycle threshold (Ct) value <35 at repeat testing. For each included subject, likelihood of reinfection was assessed by viral genomic analysis of all available specimens with a Ct value <35, structured Ct trajectory criteria, and case-by-case review by infectious diseases physicians. RESULTS: Among 1,569 individuals with repeat SARS-CoV-2 testing ≥45 days after an initial positive NAAT, 65 (4%) met cohort inclusion criteria. Viral genomic analysis characterized mutations present, and was successful for 14/65 (22%) subjects. Six subjects had genomically-supported reinfection and eight subjects had genomically-supported persistent RNA detection. Compared to viral genomic analysis, clinical and laboratory assessments correctly distinguished reinfection from persistent RNA detection in 12/14 (86%) subjects but missed 2/6 (33%) genomically-supported reinfections. CONCLUSION: Despite good overall concordance with viral genomic analysis, clinical and Ct value-based assessments failed to identify 33% of genomically-supported reinfections. Scaling-up genomic analysis for clinical use would improve detection of SARS-CoV-2 reinfections.

Infectious Diseases/Human Immunodeficiency Virus Physician Ambassadors: Advancing Policy to Improve Health.

Infectious diseases/human immunodeficiency virus (ID/HIV) physicians and other healthcare professionals advocate within the healthcare system to ensure adults and children receive effective treatment. These advocacy skills can be used to inform domestic and global infectious diseases policies to improve healthcare systems and public health. ID/HIV physicians have a unique frontline perspective to share with federal policymakers regarding how programs and policies benefit patients and public health. Providing this input is critical to the enactment of legislation that will maximize the response to infectious diseases. This article discusses the advocacy of ID/HIV physicians and other healthcare professionals in federal health policy. Key issues include funding for ID/HIV programs; the protection of public health and access to healthcare; improving research opportunities; and advancing the field of ID/HIV, including supporting the next generation of ID/HIV clinicians. The article also describes best practices for advocacy and provides case studies illustrating the impact of ID/HIV physician advocacy.

Coronavirus Disease 2019 (COVID-19) Diagnostic Clinical Decision Support: A Pre-Post Implementation Study of CORAL (COvid Risk cALculator).

BACKGROUND: Isolation of hospitalized persons under investigation (PUIs) for coronavirus disease 2019 (COVID-19) reduces nosocomial transmission risk. Efficient evaluation of PUIs is needed to preserve scarce healthcare resources. We describe the development, implementation, and outcomes of an inpatient diagnostic algorithm and clinical decision support system (CDSS) to evaluate PUIs. METHODS: We conducted a pre-post study of CORAL (COvid Risk cALculator), a CDSS that guides frontline clinicians through a risk-stratified COVID-19 diagnostic workup, removes transmission-based precautions when workup is complete and negative, and triages complex cases to infectious diseases (ID) physician review. Before CORAL, ID physicians reviewed all PUI records to guide workup and precautions. After CORAL, frontline clinicians evaluated PUIs directly using CORAL. We compared pre- and post-CORAL frequency of repeated severe acute respiratory syndrome coronavirus 2 nucleic acid amplification tests (NAATs), time from NAAT result to PUI status discontinuation, total duration of PUI status, and ID physician work hours, using linear and logistic regression, adjusted for COVID-19 incidence. RESULTS: Fewer PUIs underwent repeated testing after an initial negative NAAT after CORAL than before CORAL (54% vs 67%, respectively; adjusted odd ratio, 0.53 [95% confidence interval, .44-.63]; P < .01). CORAL significantly reduced average time to PUI status discontinuation (adjusted difference [standard error], -7.4 [0.8] hours per patient), total duration of PUI status (-19.5 [1.9] hours per patient), and average ID physician work-hours (-57.4 [2.0] hours per day) (all P < .01). No patients had a positive NAAT result within 7 days after discontinuation of precautions via CORAL. CONCLUSIONS: CORAL is an efficient and effective CDSS to guide frontline clinicians through the diagnostic evaluation of PUIs and safe discontinuation of precautions.

Updates to the Spectrum/AIM model for the UNAIDS 2020 HIV estimates.

INTRODUCTION: The Spectrum/AIM model is used by national HIV programs and UNAIDS to prepare annual estimates of key HIV indicators. This article describes key updates to paediatric and adult models for the 2021 round of HIV estimates. METHODS: Potential updates to Spectrum arise due to newly available data, new analyses of existing data, and the need for new issues to be addressed. Updates are guided by experts through the UNAIDS Reference Group on Estimates, Modelling and Projections. Changes are tested and assessed for impact before being accepted into the final model. RESULTS: Spectrum tracks children living with HIV by CD4% for ages 0-4 and CD4 count for ages 5-14. Data from IeDEA treatment sites have been used to map the transition from CD4% to CD4 count at age 5. Breastfeeding patterns in sub-Saharan Africa have been updated with the latest survey data and estimates of continuation on antiretroviral therapy (ART) with breastfeeding have been revised based on recent studies. Model assumptions about the CD4 counts of people who drop out of ART have been revised to account for CD4 count increases while on treatment. If available, monthly data on numbers on ART can now be used to estimate the effects of COVID-19-related disruptions during 2020. CONCLUSIONS: These changes are intended to provide more accurate estimates of HIV burden. The effects of these changes on paediatric indicators are small except in countries with new surveys that might have updated patterns of breastfeeding. Changes to the adult model have little effect on total new infections. AIDS-related deaths will be somewhat lower in countries that have data on ART drop out but might be increased by HIV care disruptions due to COVID-19. The updated model uses newly available data to improve the estimation of paediatric and adult HIV indicators.

Yield of Severe Acute Respiratory Syndrome Coronavirus 2 Lower Respiratory Tract Testing After a Negative Nasopharyngeal Test Among Hospitalized Persons Under Investigation for Coronavirus Disease 2019.

Among hospitalized persons under investigation for coronavirus disease 2019 (COVID-19), more repeated severe acute respiratory syndrome coronavirus 2 nucleic acid amplification tests (NAATs) after a negative NAAT were positive from lower than from upper respiratory tract specimens (1.9% vs 1.0%, P = .033). Lower respiratory testing should be prioritized among patients displaying respiratory symptoms with moderate-to-high suspicion for COVID-19 after 1 negative upper respiratory NAAT.

Outcomes from an infectious disease physician-guided evaluation of hospitalized persons under investigation for coronavirus disease 2019 (COVID-19) at a large US academic medical center.

We describe an approach to the evaluation and isolation of hospitalized persons under investigation (PUIs) for coronavirus disease 2019 (COVID-19) at a large US academic medical center. Only a small proportion (2.9%) of PUIs with 1 or more repeated severe acute respiratory coronavirus virus 2 (SARS-CoV-2) nucleic acid amplification tests (NAATs) after a negative NAAT were diagnosed with COVID-19.

Clinical, Laboratory, and Radiologic Characteristics of Patients With Initial False-Negative Severe Acute Respiratory Syndrome Coronavirus 2 Nucleic Acid Amplification Test Results.

BACKGROUND: Concerns about false-negative (FN) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid amplification tests (NAATs) have prompted recommendations for repeat testing if suspicion for coronavirus disease 2019 (COVID-19) infection is moderate to high. However, the frequency of FNs and patient characteristics associated with FNs are poorly understood. METHODS: We retrospectively reviewed test results from 15 011 adults who underwent ≥1 SARS-CoV-2 NAATs; 2699 had an initial negative NAAT and repeat testing. We defined FNs as ≥1 negative NAATs followed by a positive NAAT within 14 days during the same episode of illness. We stratified subjects with FNs by duration of symptoms before the initial FN test (≤5 days versus >5 days) and examined their clinical, radiologic, and laboratory characteristics. RESULTS: Sixty of 2699 subjects (2.2%) had a FN result during the study period. The weekly frequency of FNs among subjects with repeat testing peaked at 4.4%, coinciding with peak NAAT positivity (38%). Most subjects with FNs had symptoms (52 of 60; 87%) and chest radiography (19 of 32; 59%) consistent with COVID-19. Of the FN NAATs, 18 of 60 (30%) were performed early (ie, ≤1 day of symptom onset), and 18 of 60 (30%) were performed late (ie, >7 days after symptom onset) in disease. Among 17 subjects with 2 consecutive FNs on NP NAATs, 9 (53%) provided lower respiratory tract (LRT) specimens for testing, all of which were positive. CONCLUSIONS: Our findings support repeated NAATs among symptomatic patients, particularly during periods of higher COVID-19 incidence. The LRT testing should be prioritized to increase yield among patients with high clinical suspicion for COVID-19.

Racial and Ethnic Disparities in Disease Severity on Admission Chest Radiographs among Patients Admitted with Confirmed Coronavirus Disease 2019: A Retrospective Cohort Study.

Background Disease severity on chest radiographs has been associated with higher risk of disease progression and adverse outcomes from coronavirus disease 2019 (COVID-19). Few studies have evaluated COVID-19-related racial and/or ethnic disparities in radiology. Purpose To evaluate whether non-White minority patients hospitalized with confirmed COVID-19 infection presented with increased severity on admission chest radiographs compared with White or non-Hispanic patients. Materials and Methods This single-institution retrospective cohort study was approved by the institutional review board. Patients hospitalized with confirmed COVID-19 infection between March 17, 2020, and April 10, 2020, were identified by using the electronic medical record (n = 326; mean age, 59 years ±17 [standard deviation]; male-to-female ratio: 188:138). The primary outcome was the severity of lung disease on admission chest radiographs, measured by using the modified Radiographic Assessment of Lung Edema (mRALE) score. The secondary outcome was a composite adverse clinical outcome of intubation, intensive care unit admission, or death. The primary exposure was the racial and/or ethnic category: White or non-Hispanic versus non-White (ie, Hispanic, Black, Asian, or other). Multivariable linear regression analyses were performed to evaluate the association between mRALE scores and race and/or ethnicity. Results Non-White patients had significantly higher mRALE scores (median score, 6.1; 95% confidence interval [CI]: 5.4, 6.7) compared with White or non-Hispanic patients (median score, 4.2; 95% CI: 3.6, 4.9) (unadjusted average difference, 1.8; 95% CI: 0.9, 2.8; P < .01). For both White (adjusted hazard ratio, 1.3; 95% CI: 1.2, 1.4; P < .001) and non-White (adjusted hazard ratio, 1.2; 95% CI: 1.1, 1.3; P < .001) patients, increasing mRALE scores were associated with a higher likelihood of experiencing composite adverse outcome with no evidence of interaction (P = .16). Multivariable linear regression analyses demonstrated that non-White patients presented with higher mRALE scores at admission chest radiography compared with White or non-Hispanic patients (adjusted average difference, 1.6; 95% CI: 0.5, 2.7; P < .01). Adjustment for hypothesized mediators revealed that the association between race and/or ethnicity and mRALE scores was mediated by limited English proficiency (P < .01). Conclusion Non-White patients hospitalized with coronavirus disease 2019 infection were more likely to have a higher severity of disease on admission chest radiographs than White or non-Hispanic patients, and increased severity was associated with worse outcomes for all patients. © RSNA, 2020 Online supplemental material is available for this article.