Impact of Baseline SARS-CoV-2 Load in Plasma and Upper Airways on the Incidence of Acute Extrapulmonary Complications of COVID-19: A Multicentric, Prospective, Cohort Study
Year: 2024
Type: article
Abstract: 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.
Source: Clinical Infectious Diseases
DOI: 10.1093/cid/ciae469
Institutions: University of Copenhagen, Rigshospitalet, Centre of Excellence for Health, Immunity and Infections, University of Minnesota, Yale University, VA Connecticut Healthcare System, Icahn School of Medicine at Mount Sinai, UNSW Sydney, Kirby Institute, MRC Clinical Trials Unit at UCL, University College London, Medical Research Council, National Institutes of Health, National Institute of Allergy and Infectious Diseases, University of Cape Town, Orlando VA Medical Center, University of California, San Francisco, Frederick National Laboratory for Cancer Research
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,001
Funders: Gilead Sciences, ViiV Healthcare, National Institute for Health and Care Research, National Institutes of Health, Medical Research Council, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Allergy and Infectious Diseases, Cilag, European and Developing Countries Clinical Trials Partnership
Awards: G1234541941, ACTIV Integration of Host-targeting Therapies for COVID-19 Administrative Coordinating Center, G2035441819, G2415337126, G3899166777, G4689185066, G5107738131, G5381021697, G6983630510, G7902940806, G7903865445, Extended follow-up of randomized participants in the INSIGHT START trial
OpenAlex ID: W4402549102