Hospital-Level Variation in COVID-19 Treatment Among Hospitalized Adults in the United States: A Retrospective Cohort Study.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To characterize variation in dexamethasone and remdesivir use over time among hospitals. BACKGROUND: Little is known about hospital-level variation in COVID-19 drug treatments in a large and diverse network in the United States. METHODS: We selected individuals hospitalized with COVID-19 across 163 hospitals between February 23, 2020 and October 31, 2021 from using the HCA CHARGE, an electronic health record repository from a network of community health care facilities in the United States. We quantified receipt of dexamethasone, remdesivir, and combined use of dexamethasone and remdesivir during the hospital stay. We used 2-level logistic regression models to determine the intraclass correlation coefficient (ICC) at the hospital level, adjusting for patient and hospital characteristics. The ICC shows the proportion of total variation in drug use accounted for by hospitals. RESULTS: Among 161,667 individuals hospitalized with COVID-19, 73.0% were treated with dexamethasone, 49.1% with remdesivir, and 45.0% with both dexamethasone and remdesivir. The proportion of variation in dexamethasone use was 12.7% (adjusted ICC: 0.127), 8.5% for remdesivir, and 11.3% for combined drug use, indicating low interhospital variation. In the fully adjusted models, between-facility variation in dexamethasone use declined from 34.1% in February-March 2020 to 11.3% in January-March 2021 and then increased to 17.3% in July-October 2021. The variation in remdesivir use remained relatively stable during the study period. CONCLUSIONS: During the first 2 years of the pandemic, there was relatively consistent use of dexamethasone and remdesivir across the hospitals examined. Consistent adoption and implementation of treatment guidelines across the hospitals examined may have led to a decrease in variation in drug usage over time.

Effectiveness of Dexamethasone for COVID-19 in Hospitalized Patients with Diabetes: A Retrospective Cohort Study.

BACKGROUND: Patients with diabetes have higher mortality from COVID-19 compared to the general population. Dexamethasone, a potent glucocorticoid used for moderate to severe COVID-19, can worsen hyperglycemia in patients with diabetes, potentially leading to worse outcomes. The efficacy and safety of use of dexamethasone for COVID-19 in patients with diabetes needs further evaluation. OBJECTIVE: The study aimed to assess the efficacy and safety of dexamethasone in patients with diabetes hospitalized for COVID-19 infection. DESIGN: This retrospective study analyzed data from five hospitals in the Johns Hopkins Health System (JHHS) collected between March 3, 2020 and June 25, 2022. Propensity score matching was applied to a cohort of patients with diabetes who received dexamethasone and those who did not (controls), and outcomes were compared using Cox proportional hazards regression models. OUTCOMES: The primary outcome was time to death within 28 days. The secondary outcome was time to clinical improvement. Additional outcomes included the incidence of hyperglycemic emergencies and subgroup analysis of primary outcomes by clinical severity. RESULTS: Out of 10,329 patients admitted for COVID-19, 3,679 had diabetes, and 2,361 met the inclusion criteria. After propensity score matching, 529 patients were analyzed in each group. Survival rates between the dexamethasone and control groups during the 0-6 day and 7-28-day periods and time to clinical improvement at 28 days did not differ significantly. There was no difference in the incidence of diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS) between the groups. CONCLUSION: Dexamethasone treatment did not significantly improve survival or time to clinical improvement in patients with diabetes and COVID-19 infection. Further prospective studies are needed to confirm these findings and determine potential mechanisms.

Metagenomic next generation sequencing of plasma RNA for diagnosis of unexplained, acute febrile illness in Uganda.

Metagenomic next generation metagenomic sequencing (mNGS) has proven to be a useful tool in the diagnosis and identification of novel human pathogens and pathogens not identified on routine clinical microbiologic tests. In this study, we applied mNGS to characterize plasma RNA isolated from 42 study participants with unexplained acute febrile illness (AFI) admitted to tertiary referral hospitals in Mubende and Arua, Uganda. Study participants were selected based on clinical criteria suggestive of viral infection (i.e., thrombocytopenia, leukopenia). The study population had a median age of 28 years (IQR:24 to 38.5) and median platelet count of 114 x103 cells/mm3 (IQR:66,500 to 189,800). An average of 25 million 100 bp reads were generated per sample. We identified strong signals from diverse virus, bacteria, fungi, or parasites in 10 (23.8%) of the study participants. These included well recognized pathogens like Helicobacter pylori, human herpes virus-8, Plasmodium falciparum, Neisseria gonorrhoeae, and Rickettsia conorii. We further confirmed Rickettsia conorii infection, the cause of Mediterranean Spotted Fever (MSF), using PCR assays and Sanger sequencing. mNGS was a useful addition for detection of otherwise undetected pathogens and well-recognized non-pathogens. This is the first report to describe the molecular confirmation of a hospitalized case of MSF in sub-Saharan Africa (SSA). Further studies are needed to determine the utility of mNGS for disease surveillance in similar settings.

Precision arbovirus serology with a pan-arbovirus peptidome.

Arthropod-borne viruses represent a crucial public health threat. Current arboviral serology assays are either labor intensive or incapable of distinguishing closely related viruses, and many zoonotic arboviruses that may transition to humans lack any serologic assays. In this study, we present a programmable phage display platform, ArboScan, that evaluates antibody binding to overlapping peptides that represent the proteomes of 691 human and zoonotic arboviruses. We confirm that ArboScan provides detailed antibody binding information from animal sera, human sera, and an arthropod blood meal. ArboScan identifies distinguishing features of antibody responses based on exposure history in a Colombian cohort of Zika patients. Finally, ArboScan details epitope level information that rapidly identifies candidate epitopes with potential protective significance. ArboScan thus represents a resource for characterizing human and animal arbovirus antibody responses at cohort scale.

RNA Analysis Using Immunoassay Detection Format.

Oligonucleotide probe tagging and reverse transcriptase polymerase-chain reaction (RT-PCR) are the most widely used techniques currently used for detecting and analyzing RNA. RNA detection using labeled oligonucleotide probe-based approaches is suitable for point-of-care (POC) applications but lacks assay sensitivity, whereas RT-PCR requires complex instrumentation. As an alternative, immunoassay detection formats coupled with isothermal RNA amplification techniques have been proposed for handheld assay development. In this chapter, we describe a robust technique comprising of: (a) target RNA tagging with a complementary oligonucleotide probe labeled with a hapten moiety to form a DNA/RNA duplex hybrid; (b) complexing the DNA/RNA duplex with a pre-coated antibody (Ab) directed at the hapten moiety; (c) sandwich complex formation with an Ab that selectively recognizes the DNA/RNA structural motif; and (d) detection of the sandwich complex using a secondary Ab enzyme conjugate targeting the anti-DNA/RNA Ab followed by standard enzyme-linked immunosorbent assay (ELISA) visualization.

Self-administered versus clinician-performed BinaxNOW COVID rapid test: a comparison of accuracy.

We conducted a single-center study at a free community testing site in Baltimore City to assess the accuracy of self-performed rapid antigen tests (RATs) for COVID-19. Self-administered BinaxNOW RATs were compared with clinician-performed RATs and against a reference lab molecular testing as the gold standard. Of the 953 participants, 14.9% were positive for SARS- CoV-2 as determined by RT-PCR. The sensitivity and specificity were similar for both self- and clinician-performed RATs (sensitivity: 83.9% vs 88.2%, P = 0.40; specificity: 99.8% vs 99.6%, P = 0.6). Subgroup comparisons based on age and race yielded similar results. Notably, 5.2% (95% CI: 1.5% to 9.5%) of positive results were potentially missed due to participant misinterpretation of the self-test card. However, the false-positive rate for RATs was reassuringly comparable in accuracy to clinician-administered tests. These findings hold significant implications for physicians prescribing treatment based on patient-reported, self-administered positive test results. Our study provides robust evidence supporting the reliability and utility of patient-performed RATs, underscoring their comparable accuracy to clinician-performed RATs, and endorsing their continued use in managing COVID-19. Further studies using other rapid antigen test brands are warranted.IMPORTANCEAccurate and accessible COVID-19 testing is crucial for effective disease control and management. A recent single-center study conducted in Baltimore City examined the reliability of self-performed rapid antigen tests (RATs) for COVID-19. The study found that self-administered RATs yielded similar sensitivity and specificity to clinician-performed tests, demonstrating their comparable accuracy. These findings hold significant implications for physicians relying on patient-reported positive test results for treatment decisions. The study provides robust evidence supporting the reliability and utility of patient-performed RATs, endorsing their continued use in managing COVID-19. Furthermore, the study highlights the need for further research using different rapid antigen test brands to enhance generalizability. Ensuring affordable and widespread access to self-tests is crucial, particularly in preparation for future respiratory virus seasons and potential waves of reinfection of SARS-CoV-2 variants such as the Omicron variant.

Maternal Colonization Versus Nosocomial Transmission as the Source of Drug-Resistant Bloodstream Infection in an Indian Neonatal Intensive Care Unit: A Prospective Cohort Study.

BACKGROUND: Drug-resistant gram-negative (GN) pathogens are a common cause of neonatal sepsis in low- and middle-income countries. Identifying GN transmission patterns is vital to inform preventive efforts. METHODS: We conducted a prospective cohort study, 12 October 2018 to 31 October 2019 to describe the association of maternal and environmental GN colonization with bloodstream infection (BSI) among neonates admitted to a neonatal intensive care unit (NICU) in Western India. We assessed rectal and vaginal colonization in pregnant women presenting for delivery and colonization in neonates and the environment using culture-based methods. We also collected data on BSI for all NICU patients, including neonates born to unenrolled mothers. Organism identification, antibiotic susceptibility testing, and next-generation sequencing (NGS) were performed to compare BSI and related colonization isolates. RESULTS: Among 952 enrolled women who delivered, 257 neonates required NICU admission, and 24 (9.3%) developed BSI. Among mothers of neonates with GN BSI (n = 21), 10 (47.7%) had rectal, 5 (23.8%) had vaginal, and 10 (47.7%) had no colonization with resistant GN organisms. No maternal isolates matched the species and resistance pattern of associated neonatal BSI isolates. Thirty GN BSI were observed among neonates born to unenrolled mothers. Among 37 of 51 BSI with available NGS data, 21 (57%) showed a single nucleotide polymorphism distance of ≤5 to another BSI isolate. CONCLUSIONS: Prospective assessment of maternal GN colonization did not demonstrate linkage to neonatal BSI. Organism-relatedness among neonates with BSI suggests nosocomial spread, highlighting the importance of NICU infection prevention and control practices to reduce GN BSI.

Performance of Rapid Antigen Tests to Detect Symptomatic and Asymptomatic SARS-CoV-2 Infection : A Prospective Cohort Study.

BACKGROUND: The performance of rapid antigen tests (Ag-RDTs) for screening asymptomatic and symptomatic persons for SARS-CoV-2 is not well established. OBJECTIVE: To evaluate the performance of Ag-RDTs for detection of SARS-CoV-2 among symptomatic and asymptomatic participants. DESIGN: This prospective cohort study enrolled participants between October 2021 and January 2022. Participants completed Ag-RDTs and reverse transcriptase polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 every 48 hours for 15 days. SETTING: Participants were enrolled digitally throughout the mainland United States. They self-collected anterior nasal swabs for Ag-RDTs and RT-PCR testing. Nasal swabs for RT-PCR were shipped to a central laboratory, whereas Ag-RDTs were done at home. PARTICIPANTS: Of 7361 participants in the study, 5353 who were asymptomatic and negative for SARS-CoV-2 on study day 1 were eligible. In total, 154 participants had at least 1 positive RT-PCR result. MEASUREMENTS: The sensitivity of Ag-RDTs was measured on the basis of testing once (same-day), twice (after 48 hours), and thrice (after a total of 96 hours). The analysis was repeated for different days past index PCR positivity (DPIPPs) to approximate real-world scenarios where testing initiation may not always coincide with DPIPP 0. Results were stratified by symptom status. RESULTS: Among 154 participants who tested positive for SARS-CoV-2, 97 were asymptomatic and 57 had symptoms at infection onset. Serial testing with Ag-RDTs twice 48 hours apart resulted in an aggregated sensitivity of 93.4% (95% CI, 90.4% to 95.9%) among symptomatic participants on DPIPPs 0 to 6. When singleton positive results were excluded, the aggregated sensitivity on DPIPPs 0 to 6 for 2-time serial testing among asymptomatic participants was lower at 62.7% (CI, 57.0% to 70.5%), but it improved to 79.0% (CI, 70.1% to 87.4%) with testing 3 times at 48-hour intervals. LIMITATION: Participants tested every 48 hours; therefore, these data cannot support conclusions about serial testing intervals shorter than 48 hours. CONCLUSION: The performance of Ag-RDTs was optimized when asymptomatic participants tested 3 times at 48-hour intervals and when symptomatic participants tested 2 times separated by 48 hours. PRIMARY FUNDING SOURCE: National Institutes of Health RADx Tech program.

Using machine learning on clinical data to identify unexpected patterns in groups of COVID-19 patients.

As clinicians are faced with a deluge of clinical data, data science can play an important role in highlighting key features driving patient outcomes, aiding in the development of new clinical hypotheses. Insight derived from machine learning can serve as a clinical support tool by connecting care providers with reliable results from big data analysis that identify previously undetected clinical patterns. In this work, we show an example of collaboration between clinicians and data scientists during the COVID-19 pandemic, identifying sub-groups of COVID-19 patients with unanticipated outcomes or who are high-risk for severe disease or death. We apply a random forest classifier model to predict adverse patient outcomes early in the disease course, and we connect our classification results to unsupervised clustering of patient features that may underpin patient risk. The paradigm for using data science for hypothesis generation and clinical decision support, as well as our triaged classification approach and unsupervised clustering methods to determine patient cohorts, are applicable to driving rapid hypothesis generation and iteration in a variety of clinical challenges, including future public health crises.

Characterizing SARS-CoV-2 Transcription of Subgenomic and Genomic RNAs During Early Human Infection Using Multiplexed Droplet Digital Polymerase Chain Reaction.

BACKGROUND: Control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission requires understanding SARS-CoV-2 replication dynamics. METHODS: We developed a multiplexed droplet digital polymerase chain reaction (ddPCR) assay to quantify SARS-CoV-2 subgenomic RNAs (sgRNAs), which are only produced during active viral replication, and discriminate them from genomic RNAs (gRNAs). We applied the assay to specimens from 144 people with single nasopharyngeal samples and 27 people with >1 sample. Results were compared to quantitative PCR (qPCR) and viral culture. RESULTS: sgRNAs were quantifiable across a range of qPCR cycle threshold (Ct) values and correlated with Ct values. The ratio sgRNA:gRNA was stable across a wide range of Ct values, whereas adjusted amounts of N sgRNA to a human housekeeping gene declined with higher Ct values. Adjusted sgRNA and gRNA amounts were quantifiable in culture-negative samples, although levels were significantly lower than in culture-positive samples. Daily testing of 6 persons revealed that sgRNA is concordant with culture results during the first week of infection but may be discordant with culture later in infection. sgRNA:gRNA is constant during infection despite changes in viral culture. CONCLUSIONS: Ct values from qPCR correlate with active viral replication. More work is needed to understand why some cultures are negative despite presence of sgRNA.

Impact of Severe Acute Respiratory Syndrome Coronavirus 2 Variants on Inpatient Clinical Outcome.

BACKGROUND: Prior observation has shown differences in COVID-19 hospitalization risk between SARS-CoV-2 variants, but limited information describes hospitalization outcomes. METHODS: Inpatients with COVID-19 at 5 hospitals in the eastern United States were included if they had hypoxia, tachypnea, tachycardia, or fever, and SARS-CoV-2 variant data, determined from whole-genome sequencing or local surveillance inference. Analyses were stratified by history of SARS-CoV-2 vaccination or infection. The average effect of SARS-CoV-2 variant on 28-day risk of severe disease, defined by advanced respiratory support needs, or death was evaluated using models weighted on propensity scores derived from baseline clinical features. RESULTS: Severe disease or death within 28 days occurred for 977 (29%) of 3369 unvaccinated patients and 269 (22%) of 1230 patients with history of vaccination or prior SARS-CoV-2 infection. Among unvaccinated patients, the relative risk of severe disease or death for Delta variant compared with ancestral lineages was 1.30 (95% confidence interval [CI]: 1.11-1.49). Compared with Delta, the risk for Omicron patients was .72 (95% CI: .59-.88) and compared with ancestral lineages was .94 (.78-1.1). Among Omicron and Delta infections, patients with history of vaccination or prior SARS-CoV-2 infection had half the risk of severe disease or death (adjusted hazard ratio: .40; 95% CI: .30-.54), but no significant outcome difference by variant. CONCLUSIONS: Although risk of severe disease or death for unvaccinated inpatients with Omicron was lower than with Delta, it was similar to ancestral lineages. Severe outcomes were less common in vaccinated inpatients, with no difference between Delta and Omicron infections.

Aetiology of hospitalized fever and risk of death at Arua and Mubende tertiary care hospitals in Uganda from August 2019 to August 2020.

BACKGROUND: Epidemiology of febrile illness in Uganda is shifting due to increased HIV treatment access, emerging viruses, and increased surveillance. We investigated the aetiology and outcomes of acute febrile illness in adults presenting to hospital using a standardized testing algorithm of available assays in at Arua and Mubende tertiary care hospitals in Uganda. METHODS: We recruited adults with a ≥ 38.0 °C temperature or history of fever within 48 h of presentation from August 2019 to August 2020. Medical history, demographics, and vital signs were recorded. Testing performed included a complete blood count, renal and liver function, malaria smears, blood culture, and human immunodeficiency virus (HIV). When HIV positive, testing included cryptococcal antigen, CD4 count, and urine lateral flow lipoarabinomannan assay for tuberculosis. Participants were followed during hospitalization and at a 1-month visit. A Cox proportional hazard regression was performed to evaluate for baseline clinical features and risk of death. RESULTS: Of 132 participants, the median age was 33.5 years (IQR 24 to 46) and 58.3% (n = 77) were female. Overall, 73 (55.3%) of 132 had a positive microbiologic result. Among those living with HIV, 31 (68.9%) of 45 had at least one positive assay; 16 (35.6%) had malaria, 14 (31.1%) tuberculosis, and 4 (8.9%) cryptococcal antigenemia. The majority (65.9%) were HIV-negative; 42 (48.3%) of 87 had at least one diagnostic assay positive; 24 (27.6%) had positive malaria smears and 1 was Xpert MTB/RIF Ultra positive. Overall, 16 (12.1%) of 132 died; 9 (56.3%) of 16 were HIV-negative, 6 died after discharge. High respiratory rate (≥ 22 breaths per minute) (hazard ratio [HR] 8.05; 95% CI 1.81 to 35.69) and low (i.e., < 92%) oxygen saturation (HR 4.33; 95% CI 1.38 to 13.61) were identified to be associated with increased risk of death. CONCLUSION: In those with hospitalized fever, malaria and tuberculosis were common causes of febrile illness, but most deaths were non-malarial, and most HIV-negative participants did not have a positive diagnostic result. Those with respiratory failure had a high risk of death.

Anti-PF4 antibodies associated with disease severity in COVID-19.

Severe COVID-19 is characterized by a prothrombotic state associated with thrombocytopenia, with microvascular thrombosis being almost invariably present in the lung and other organs at postmortem examination. We evaluated the presence of antibodies to platelet factor 4 (PF4)-polyanion complexes using a clinically validated immunoassay in 100 hospitalized patients with COVID-19 with moderate or severe disease (World Health Organization score, 4 to 10), 25 patients with acute COVID-19 visiting the emergency department, and 65 convalescent individuals. Anti-PF4 antibodies were detected in 95 of 100 hospitalized patients with COVID-19 (95.0%) irrespective of prior heparin treatment, with a mean optical density value of 0.871 ± 0.405 SD (range, 0.177 to 2.706). In contrast, patients hospitalized for severe acute respiratory disease unrelated to COVID-19 had markedly lower levels of the antibodies. In a high proportion of patients with COVID-19, levels of all three immunoglobulin (Ig) isotypes tested (IgG, IgM, and IgA) were simultaneously elevated. Antibody levels were higher in male than in female patients and higher in African Americans and Hispanics than in White patients. Anti-PF4 antibody levels were correlated with the maximum disease severity score and with significant reductions in circulating platelet counts during hospitalization. In individuals convalescent from COVID-19, the antibody levels returned to near-normal values. Sera from patients with COVID-19 induced higher levels of platelet activation than did sera from healthy blood donors, but the results were not correlated with the levels of anti-PF4 antibodies. These results demonstrate that the vast majority of patients with severe COVID-19 develop anti-PF4 antibodies, which may play a role in the clinical complications of COVID-19.

Reducing misclassification bias in severe malaria research.

By incorporating platelets and PfHRP2 into standard case definitions of severe falciparum malaria, Watson et al.1 increased diagnostic specificity to 93%. The approach trades off sensitivity and might introduce a selection bias but offers a helpful way to handle misclassification.

Longitudinal Analysis of SARS-CoV-2 Vaccine Breakthrough Infections Reveals Limited Infectious Virus Shedding and Restricted Tissue Distribution.

Background: The global effort to vaccinate people against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during an ongoing pandemic has raised questions about how vaccine breakthrough infections compare with infections in immunologically naive individuals and the potential for vaccinated individuals to transmit the virus. Methods: We examined viral dynamics and infectious virus shedding through daily longitudinal sampling in 23 adults infected with SARS-CoV-2 at varying stages of vaccination, including 6 fully vaccinated individuals. Results: The durations of both infectious virus shedding and symptoms were significantly reduced in vaccinated individuals compared with unvaccinated individuals. We also observed that breakthrough infections are associated with strong tissue compartmentalization and are only detectable in saliva in some cases. Conclusions: Vaccination shortens the duration of time of high transmission potential, minimizes symptom duration, and may restrict tissue dissemination.

Thromboprophylaxis in people hospitalized with COVID-19: Assessing intermediate or standard doses in a retrospective cohort study.

Background and Objectives: Current clinical guidelines recommend thromboprophylaxis for adults hospitalized with coronavirus disease 2019 (COVID-19), yet it is unknown whether higher doses of thromboprophylaxis offer benefits beyond standard doses. Methods: We studied electronic health records from 50 091 adults hospitalized with COVID-19 in the United States between February 2020 and February 2021. We compared standard (enoxaparin 30 or 40 mg/day, fondaparinux 2.5 mg, or heparin 5000 units twice or thrice per day) versus intermediate (enoxaparin 30 or 40 mg twice daily, or up to 1.2 mg/kg of body weight daily, heparin 7500 units thrice per day or heparin 10 000 units twice or thrice per day) thromboprophylaxis. We separately examined risk of escalation to therapeutic anticoagulation, severe disease (first occurrence of high-flow nasal cannula, noninvasive positive pressure ventilation or invasive mechanical ventilation), and death. To summarize risk, we present hazard ratios (HRs) with 95% confidence intervals (CIs) using adjusted time-dependent Cox proportional hazards regression models. Results: People whose first dose was high intensity were younger, more often obese, and had greater oxygen support requirements. Intermediate dose thromboprophylaxis was associated with increased risk of therapeutic anticoagulation (HR, 3.39; 95% CI, 3.22-3.57), severe disease (HR, 1.22; 95% CI, 1.17-1.28), and death (HR, 1.37; 95% CI, 1.21-1.55). Increased risks associated with intermediate-dose thromboprophylaxis persisted in subgroup and sensitivity analyses varying populations and definitions of exposures, outcomes, and covariates. Conclusions: Our findings do not support routine use of intermediate-dose thromboprophylaxis to prevent clinical worsening, severe disease, or death among adults hospitalized with COVID-19.

Limitations of Molecular and Antigen Test Performance for SARS-CoV-2 in Symptomatic and Asymptomatic COVID-19 Contacts.

COVID-19 has brought unprecedented attention to the crucial role of diagnostics in pandemic control. We compared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test performance by sample type and modality in close contacts of SARS-CoV-2 cases. Close contacts of SARS-CoV-2-positive individuals were enrolled after informed consent. Clinician-collected nasopharyngeal (NP) swabs in viral transport media (VTM) were tested with a routine clinical reference nucleic acid test (NAT) and PerkinElmer real-time reverse transcription-PCR (RT-PCR) assay; positive samples were tested for infectivity using a VeroE6TMPRSS2 cell culture model. Self-collected passive drool was also tested using the PerkinElmer RT-PCR assay. For the first 4 months of study, midturbinate swabs were tested using the BD Veritor rapid antigen test. Between 17 November 2020 and 1 October 2021, 235 close contacts of SARS-CoV-2 cases were recruited, including 95 with symptoms (82% symptomatic for ≤5 days) and 140 asymptomatic individuals. Reference NATs were positive for 53 (22.6%) participants; 24/50 (48%) were culture positive. PerkinElmer testing of NP and saliva samples identified an additional 28 (11.9%) SARS-CoV-2 cases who tested negative by reference NAT. Antigen tests performed for 99 close contacts showed 83% positive percent agreement (PPA) with reference NAT among early symptomatic persons, but 18% PPA in others; antigen tests in 8 of 11 (72.7%) culture-positive participants were positive. Contacts of SARS-CoV-2 cases may be falsely negative early after contact, but more sensitive platforms may identify these cases. Repeat or serial SARS-CoV-2 testing with both antigen and molecular assays may be warranted for individuals with high pretest probability for infection.

Racial and Ethnic Discrepancy in Pulse Oximetry and Delayed Identification of Treatment Eligibility Among Patients With COVID-19.

Importance: Pulse oximetry guides triage and therapy decisions for COVID-19. Whether reported racial inaccuracies in oxygen saturation measured by pulse oximetry are present in patients with COVID-19 and associated with treatment decisions is unknown. Objective: To determine whether there is differential inaccuracy of pulse oximetry by race or ethnicity among patients with COVID-19 and estimate the association of such inaccuracies with time to recognition of eligibility for oxygen threshold-specific COVID-19 therapies. Design, Setting, and Participants: This retrospective cohort study of clinical data from 5 referral centers and community hospitals in the Johns Hopkins Health System included patients with COVID-19 who self-identified as Asian, Black, Hispanic, or White. Exposures: Concurrent measurements (within 10 minutes) of oxygen saturation levels in arterial blood (SaO2) and by pulse oximetry (SpO2). Main Outcomes and Measures: For patients with concurrent SpO2 and SaO2 measurements, the proportion with occult hypoxemia (SaO2<88% with concurrent SpO2 of 92%-96%) was compared by race and ethnicity, and a covariate-adjusted linear mixed-effects model was produced to estimate the association of race and ethnicity with SpO2 and SaO2 difference. This model was applied to identify a separate sample of patients with predicted SaO2 levels of 94% or less before an SpO2 level of 94% or less or oxygen treatment initiation. Cox proportional hazards models were used to estimate differences by race and ethnicity in time to recognition of eligibility for guideline-recommended COVID-19 therapies, defined as an SpO2 level of 94% or less or oxygen treatment initiation. The median delay among individuals who ultimately had recognition of eligibility was then compared. Results: Of 7126 patients with COVID-19, 1216 patients (63 Asian [5.2%], 478 Black [39.3%], 215 Hispanic [17.7%], and 460 White [37.8%] individuals; 507 women [41.7%]) had 32 282 concurrently measured SpO2 and SaO2. Occult hypoxemia occurred in 19 Asian (30.2%), 136 Black (28.5%), and 64 non-Black Hispanic (29.8%) patients compared with 79 White patients (17.2%). Compared with White patients, SpO2 overestimated SaO2 by an average of 1.7% among Asian (95% CI, 0.5%-3.0%), 1.2% among Black (95% CI, 0.6%-1.9%), and 1.1% among non-Black Hispanic patients (95% CI, 0.3%-1.9%). Separately, among 1903 patients with predicted SaO2 levels of 94% or less before an SpO2 level of 94% or less or oxygen treatment initiation, compared with White patients, Black patients had a 29% lower hazard (hazard ratio, 0.71; 95% CI, 0.63-0.80), and non-Black Hispanic patients had a 23% lower hazard (hazard ratio, 0.77; 95% CI, 0.66-0.89) of treatment eligibility recognition. A total of 451 patients (23.7%) never had their treatment eligibility recognized, most of whom (247 [54.8%]) were Black. Among the remaining 1452 (76.3%) who had eventual recognition of treatment eligibility, Black patients had a median delay of 1.0 hour (95% CI, 0.23-1.9 hours; P = .01) longer than White patients. There was no significant median difference in delay between individuals of other racial and ethnic minority groups and White patients. Conclusions and Relevance: The results of this cohort study suggest that racial and ethnic biases in pulse oximetry accuracy were associated with greater occult hypoxemia in Asian, Black, and non-Black Hispanic patients with COVID-19, which was associated with significantly delayed or unrecognized eligibility for COVID-19 therapies among Black and Hispanic patients. This disparity may contribute to worse outcomes among Black and Hispanic patients with COVID-19.