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Persistent Low-Grade Inflammation and Post-COVID Condition: Evidence from the ORCHESTRA Cohort.

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Persistent low-grade inflammation, indicated by elevated C-reactive protein (CRP), is linked to the respiratory phenotype of post-COVID condition (PCC) up to 18 months. Early COVID-19 infection severity correlates with follow-up inflammation markers.

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Area of Science:

  • Immunology
  • Infectious Diseases
  • Clinical Biochemistry

Background:

  • Post-COVID condition (PCC) may involve persistent low-grade inflammation, affecting laboratory test results.
  • The diagnostic and follow-up utility of routine lab tests for PCC remains under investigation.

Purpose of the Study:

  • To investigate biochemical marker alterations in relation to distinct PCC phenotypes up to 18 months post-SARS-CoV-2 infection.
  • To assess the correlation between acute infection biochemistry and subsequent PCC development.
  • To evaluate the link between acute infection severity and follow-up biochemical abnormalities.

Main Methods:

  • Prospective, multinational cohort study (ORCHESTRA) with 4587 SARS-CoV-2 patients followed for 18 months.
  • Multivariable analysis of blood tests collected during acute infection and at 6, 12, and 18 months.
  • Identification of four PCC phenotypes (RESc, CPc, CFc, NSc) using principal component analysis.

Main Results:

  • Patients with PCC, particularly the respiratory (RESc) phenotype, showed significantly higher C-reactive protein (CRP) levels at 12 and 18 months compared to controls.
  • CRP levels in PCC and RESc patients consistently exceeded 3 mg/L, indicating low-grade inflammation.
  • Acute COVID-19 severity correlated with elevated CRP, ferritin, and LDH during follow-up; early biochemical abnormalities did not predict PCC development.

Conclusions:

  • Blood test abnormalities consistent with sustained low-grade inflammation are detectable up to 18 months in the RESc PCC phenotype.
  • These findings support a role for prolonged inflammation in the pathogenesis of PCC.
  • Clinical trials targeting anti-inflammatory therapies and symptom-specific interventions for RESc patients are warranted.