Coronavirus Disease 2019 Temperature Trajectories Correlate With Hyperinflammatory and Hypercoagulable Subphenotypes.

Area of Science:

• Infectious Diseases
• Immunology
• Critical Care Medicine

Background:

• Body temperature patterns in infected patients correlate with immune responses and survival.
• Understanding these patterns in coronavirus disease 2019 (COVID-19) is crucial for patient management.

Purpose of the Study:

• To associate distinct body temperature trajectories in hospitalized COVID-19 patients with specific clinical manifestations and outcomes.
• To identify potential subphenotypes within COVID-19 based on temperature patterns.

Main Methods:

• A retrospective observational study included 5,903 adult COVID-19 patients from four hospitals.
• Patients were classified into four temperature subphenotypes (hyperthermic slow resolvers, hyperthermic fast resolvers, normothermics, hypothermics) using trajectory modeling based on initial 72-hour temperature data.
• Clinical characteristics, biomarkers, and outcomes were compared across subphenotypes.

Main Results:

• Four subphenotypes were identified: hypothermics (15%), normothermics (36%), hyperthermic fast resolvers (25%), and hyperthermic slow resolvers (25%).
• Hypothermics exhibited abnormal coagulation markers (e.g., high d-dimer) and a higher prevalence of cerebrovascular accidents and venous thromboembolism.
• Hyperthermic slow resolvers showed elevated inflammatory markers (e.g., C-reactive protein, ferritin, IL-6) and increased odds of mechanical ventilation, vasopressors, and 30-day mortality.
• The prevalence of hyperthermic slow resolvers decreased significantly over time, from 53% to <15%, coinciding with increased dexamethasone use, which was associated with a 27% reduction in their membership.

Conclusions:

• COVID-19 patients can be categorized into distinct temperature-related subphenotypes with differing clinical profiles.
• Hypothermic patients may represent a hypercoagulable state, while hyperthermic slow resolvers suggest a hyperinflammatory state.
• Further research is needed to explore targeted antithrombotic and anti-inflammatory therapies for these temperature-defined subphenotypes.