The Association of Baseline Plasma SARS-CoV-2 Nucleocapsid Antigen Level and Outcomes in Patients Hospitalized With COVID-19.

BACKGROUND: Levels of plasma SARS-CoV-2 nucleocapsid (N) antigen may be an important biomarker in patients with COVID-19 and enhance our understanding of the pathogenesis of COVID-19. OBJECTIVE: To evaluate whether levels of plasma antigen can predict short-term clinical outcomes and identify clinical and viral factors associated with plasma antigen levels in hospitalized patients with SARS-CoV-2. DESIGN: Cross-sectional study of baseline plasma antigen level from 2540 participants enrolled in the TICO (Therapeutics for Inpatients With COVID-19) platform trial from August 2020 to November 2021, with additional data on day 5 outcome and time to discharge. SETTING: 114 centers in 10 countries. PARTICIPANTS: Adults hospitalized for acute SARS-CoV-2 infection with 12 days or less of symptoms. MEASUREMENTS: Baseline plasma viral N antigen level was measured at a central laboratory. Delta variant status was determined from baseline nasal swabs using reverse transcriptase polymerase chain reaction. Associations between baseline patient characteristics and viral factors and baseline plasma antigen levels were assessed using both unadjusted and multivariable modeling. Association between elevated baseline antigen level of 1000 ng/L or greater and outcomes, including worsening of ordinal pulmonary scale at day 5 and time to hospital discharge, were evaluated using logistic regression and Fine-Gray regression models, respectively. RESULTS: Plasma antigen was below the level of quantification in 5% of participants at enrollment, and 1000 ng/L or greater in 57%. Baseline pulmonary severity of illness was strongly associated with plasma antigen level, with mean plasma antigen level 3.10-fold higher among those requiring noninvasive ventilation or high-flow nasal cannula compared with room air (95% CI, 2.22 to 4.34). Plasma antigen level was higher in those who lacked antispike antibodies (6.42 fold; CI, 5.37 to 7.66) and in those with the Delta variant (1.73 fold; CI, 1.41 to 2.13). Additional factors associated with higher baseline antigen level included male sex, shorter time since hospital admission, decreased days of remdesivir, and renal impairment. In contrast, race, ethnicity, body mass index, and immunocompromising conditions were not associated with plasma antigen levels. Plasma antigen level of 1000 ng/L or greater was associated with a markedly higher odds of worsened pulmonary status at day 5 (odds ratio, 5.06 [CI, 3.41 to 7.50]) and longer time to hospital discharge (median, 7 vs. 4 days; subhazard ratio, 0.51 [CI, 0.45 to 0.57]), with subhazard ratios similar across all levels of baseline pulmonary severity. LIMITATIONS: Plasma samples were drawn at enrollment, not hospital presentation. No point-of-care test to measure plasma antigen is currently available. CONCLUSION: Elevated plasma antigen is highly associated with both severity of pulmonary illness and clinically important patient outcomes. Multiple clinical and viral factors are associated with plasma antigen level at presentation. These data support a potential role of ongoing viral replication in the pathogenesis of SARS-CoV-2 in hospitalized patients. PRIMARY FUNDING SOURCE: U.S. government Operation Warp Speed and National Institute of Allergy and Infectious Diseases.

Front-Line Emergency Department Clinician Acceptability and Use of a Prototype Real-Time Cloud-Based Influenza Surveillance System.

Objectives: To assess emergency department (ED) clinicians' perceptions of a novel real-time influenza surveillance system using a pre- and post-implementation structured survey. Methods: We created and implemented a laboratory-based real-time influenza surveillance system at two EDs at the beginning of the 2013-2014 influenza season. Patients with acute respiratory illness were tested for influenza using rapid PCR-based Cepheid Xpert Flu assay. Results were instantaneously uploaded to a cloud-based data aggregation system made available to clinicians via a web-based dashboard. Clinicians received bimonthly email updates summating year-to-date results. Clinicians were surveyed prior to, and after the influenza season, to assess their views regarding acceptability and utility of the surveillance system data which were shared via dashboard and email updates. Results: The pre-implementation survey revealed that the majority (82%) of the 151 ED clinicians responded that they "sporadically" or "don't," actively seek influenza-related information during the season. However, most (75%) reported that they would find additional information regarding influenza prevalence useful. Following implementation, there was an overall increase in the frequency of clinician self-reporting increased access to surveillance information from 50 to 63%, with the majority (75%) indicating that the surveillance emails impacted their general awareness of influenza. Clinicians reported that the additional real-time surveillance data impacted their testing (65%) and treatment (51%) practices. Conclusions: The majority of ED clinicians found surveillance data useful and indicated the additional information impacted their clinical practice. Accurate and timely surveillance information, distributed in a provider-friendly format could impact ED clinician management of patients with suspected influenza.