Post-Acute Sequelae of COVID-19 Persist Over 3 Years in Acute Lung Injury/Acute Respiratory Distress Syndrome Survivors But Are Not Associated With Persistent Thromboinflammation or Endothelial Dysfunction.

PASC was present in 26% of participants at both 15 months and 3 years after hospitalization for severe COVID-19 ALI/ARDS.

• PASC presence was defined using the 12 symptoms and scoring from the Researching COVID to Enhance Recovery (RECOVER) definition.
• The cohort consisted of 150 adult survivors of severe and critical COVID-19 from the first wave of the pandemic.
• Sampling was weighted to include 50% survivors of mechanical ventilation.
• The prevalence of PASC remained stable at 26% at both the 15-month and 3-year timepoints.

PASC and symptom phenotypes at 15 months and 3 years were consistently associated with higher frailty phenotype category, worse short physical performance battery scores, and shorter 6-minute walk distance.

• Physical function measures assessed included frailty phenotype category, short physical performance battery scores, and 6-minute walk distance.
• Associations with physical function measures were consistent across both the 15-month and 3-year follow-up timepoints.
• Symptom phenotypes examined included post-exertional malaise, fatigue, and brain fog.
• Analyses were adjusted for age, sex, body mass index, comorbidities, and days since COVID-19 diagnosis.

Biomarkers of inflammation, endothelial function, and complement were not associated with PASC or symptom phenotypes in cross-sectional or longitudinal analyses.

• Eleven serum biomarkers were measured at hospital discharge, 4 months, 15 months, and 3 years.
• Inflammatory biomarkers tested included interleukin-6 and soluble tumor necrosis factor receptor-1.
• Endothelial function biomarkers included angiopoietin.
• Complement biomarkers included C2, C4b, and C5.
• No associations were found in either cross-sectional or longitudinal analyses after adjusting for age, sex, body mass index, comorbidities, and days since COVID-19 diagnosis.

The study cohort was predominantly Hispanic and Black, with a mean age of 56 years.

• The mean (sd) age of the cohort was 56 years (13).
• 67% of participants were Hispanic and 25% were Black.
• The cohort included 150 adult survivors from a single center during the first wave of the pandemic.
• The study was a single-center prospective cohort design with sampling weighted to include 50% survivors of mechanical ventilation.

Inflammation, endothelial dysfunction, and complement activation were identified in the background literature as associated with COVID-19 acute lung injury and ARDS severity.

• The study hypothesized that higher levels of inflammation, endothelial dysfunction, and complement activation implicated in more severe COVID-19 ALI/ARDS would be associated with PASC phenotypes.
• These biomarkers were previously implicated in worse short-term outcomes in acute COVID-19, non-COVID-19 ARDS, and sepsis.
• The hypothesis was not supported by the study findings.