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Updated: Jul 6, 2025

Lung CT Segmentation to Identify Consolidations and Ground Glass Areas for Quantitative Assesment of SARS-CoV Pneumonia
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Features of acute COVID-19 associated with post-acute sequelae of SARS-CoV-2 phenotypes: results from the IMPACC

Al Ozonoff1, Naresh Doni Jayavelu2, Shanshan Liu1

  • 1Clinical & Data Coordinating Center (CDCC), Precision Vaccines Program, Boston Children's Hospital, Boston, MA, USA.

Nature Communications
|January 3, 2024
PubMed

Insights

Post-acute sequelae of SARS-CoV-2 (PASC) presents diverse symptoms, clustering into physical, mental/cognitive, or multidomain deficits. Early viral load and immune responses correlate with specific PASC subtypes, informing future treatments.

Area of Science:

  • Immunology
  • Infectious Diseases
  • Public Health

Background:

  • Post-acute sequelae of SARS-CoV-2 (PASC) represents a significant and complex public health challenge.
  • Understanding the heterogeneous clinical presentations and underlying biological factors of PASC is crucial for effective management.

Purpose of the Study:

  • To characterize patient-reported outcomes (PROs) and identify distinct clusters of PASC symptoms.
  • To investigate associations between acute-phase SARS-CoV-2 infection characteristics and PASC sub-phenotypes.
  • To explore potential immunological and molecular correlates of different PASC presentations.

Main Methods:

  • Prospective assessment of 590 participants from hospital admission for COVID-19 through one year post-discharge.
  • Latent profile analysis to model clusters of patient-reported outcomes based on reported deficits.
  • Mass cytometry (CyTOF) to analyze circulating B lymphocyte frequency.
  • Measurement of circulating fibroblast growth factor 21 (FGF21) levels.

Main Results:

  • Four PRO clusters were identified: minimal, physical, mental/cognitive, and multidomain deficits, highlighting PASC heterogeneity.
  • PASC sub-phenotypes were associated with female sex and specific comorbidities.
  • Higher acute respiratory SARS-CoV-2 viral burden and lower antibody titers correlated with physical and multidomain PASC clusters.
  • Lower B lymphocyte frequency was observed in the multidomain cluster.
  • Elevated FGF21 levels were found in mental/cognitive and multidomain PASC clusters.

Conclusions:

  • PASC exhibits diverse clinical presentations, with identifiable sub-phenotypes linked to host factors and acute infection characteristics.
  • Immune dysregulation, including B cell alterations and elevated FGF21, may contribute to specific PASC manifestations.
  • Linking acute anti-viral host responses to PASC development is essential for targeted therapeutic strategies and prevention.

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