Respiratory burden in post-acute COVID-19 sequelae: a longitudinal study of airway and systemic inflammation and clinical outcomes. Journal Articles uri icon

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abstract

  • BACKGROUND: It is unclear why patients with post-acute coronavirus disease 2019 sequelae (PACS) often present with persistent respiratory symptoms. We hypothesised that autoimmune inflammatory biomarkers may be associated with the persistence and/or resolution of these symptoms. We performed symptom-based unsupervised cluster analysis to evaluate airway and systemic immune responses in PACS participants over time. METHODS: Individuals with confirmed SARS-CoV-2 infection, a persistent range of PACS symptoms for >12 weeks and no previous diagnosis of chronic lung disease were recruited and assessed at a 6-month follow-up. Assessments included St George's Respiratory Questionnaire (SGRQ), pulmonary function testing, 6-min walk test and analysis of blood and sputum inflammatory markers. RESULTS: Unsupervised clustering based on SGRQ domains of 85 PACS individuals revealed four clusters. Cluster 1 (14%) reported no impairment and normal lung function, whereas clusters 2 (24%) and 3 (36%) were moderately symptomatic. Cluster 3 had a greater proportion of reduced lung function. Cluster 4 (26%) reported severe impairment across all SGRQ domains, with significantly lower 6-min walk distance, dyspnoea and fatigue. Clusters 3 and 4 had evidence of systemic inflammation (C-reactive protein and anti-SS-B/La). Sputum analysis showed no evidence of airway inflammation in any cluster. After 6 months, improved symptoms in 43% of individuals correlated with increased forced expiratory volume in 1 s percentage predicted and low serum interleukin-8 (p<0.05) over time. Multivariate regression suggested that a reduction in serum anti-SS-B/La IgG over 6 months was associated with improvement of SGRQ impact (t=3.17, p=0.003) and activity (t=2.04, p=0.005). CONCLUSIONS: A subset of previously healthy PACS patients have clinically relevant respiratory burden as identified by unbiased SGRQ domain analysis associated with systemic inflammation and autoantibodies.

authors

  • Chiu, Mei Nee
  • Chowdhury, Abhiroop
  • Zhang, Kayla
  • Somalwar, Snehal
  • Jamil, Rameen
  • Thakar, Ashutosh
  • Sidhom, Karen
  • Sedhom, Nardien
  • Thanavala, Neel
  • Mukherjee, Manan
  • Kjarsgaard, Melanie
  • Venegas, Carmen Garrido
  • Radadia, Nisarg
  • Tan, Nadia S
  • Patel, Zil
  • Ahammed, Nabila
  • Isshiki, Takuma
  • Nolasco, Santi
  • Chagla, Zain
  • Kolb, Martin
  • Duong, Mylinh
  • Gershon, Andrea S
  • Nair, Parameswaran
  • Satia, Imran
  • Tselios, Konstantinos
  • Ho, Terence
  • Balakrishnan, Narayanaswamy
  • Svenningsen, Sarah
  • Mukherjee, Manali

publication date

  • May 2025