Search

Background Extrapulmonary complications (EPCs) are common in patients hospitalized for coronavirus disease 2019 (COVID-19), but data on their clinical consequences and association with viral replication and systemic viral dissemination are lacking. Methods Patients hospitalized for COVID-19 and enrolled in the Therapeutics for Inpatients with COVID-19 (TICO) platform trial at 114 international sites between August 2020 and November 2021 were included in a prospective cohort study. We categorized EPCs into 39 event types within 9 categories and estimated their frequency through day 28 and their association with clinical outcomes through day 90. We analyzed the association between baseline viral burden (plasma nucleocapsid antigen [N-Ag] level and upper airway viral load) and EPCs, adjusting for other baseline factors. Results A total of 2625 trial participants were included in the study. Their median age was 57 years (interquartile range, 46–68 years), 57.7% were male, and 537 (20.5%) had ≥1 EPC. EPCs were associated with higher day-90 all-cause mortality rate (hazard ratio, 9.6 [95% confidence interval, 7.3–12.7]) after adjustment for other risk factors. The risk of EPCs increased with increasing baseline plasma N-Ag level (hazard ratio, 1.21 per log10 ng/L increase [95% confidence interval, 1.09–1.34]), and upper airway viral load (1.12 per log10 copies/mL increase [1.04–1.19), after adjustment for comorbid conditions, disease severity, inflammatory markers, and other baseline factors. Trial treatment allocation had no effect on EPC risk. Conclusions Systemic viral dissemination as evidenced by high plasma N-Ag level and high respiratory viral burden are associated with development of EPCs in COVID-19, which in turn are associated with higher 90-day mortality rates. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]