Annals of Internal MedicineDifferentiation of Prior SARS-CoV-2 Infection and Postacute Sequelae by Standard Clinical Laboratory Measurements in the RECOVER Cohort

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A comprehensive study involving more than 10,000 participants has found that routine clinical laboratory tests are not effective in identifying reliable biomarkers for postacute sequelae of SARS-CoV-2 infection (PASC), commonly known as long COVID. The research, published in the Annals of Internal Medicine, examined 25 standard clinical laboratory measurements and their potential to differentiate between individuals with and without prior SARS-CoV-2 infection, as well as those with and without PASC symptoms.

Key Points:

• The study included 8,746 participants with prior SARS-CoV-2 infection and 1,348 uninfected participants.
• Among those with prior infection, 21.5% had a PASC index of 12 or higher, while 38.3% had a PASC index of zero.
• No clinically meaningful differences were found in mean laboratory values between those with a PASC index ≥12 and those with a PASC index of zero.
• Small differences were observed between those with and without prior infection:
  • Lower mean platelet count in those with prior infection (265.9 × 10^9 cells/L vs. 275.2 × 10^9 cells/L)
  • Higher mean HbA1c level in those with prior infection (5.58% vs. 5.46%)
  • Higher urinary albumin-creatinine ratio (uACR) in those with prior infection (81.9 mg/g vs. 43.0 mg/g)
• The difference in HbA1c levels was attenuated after excluding participants with preexisting diabetes.
• The small difference in platelet count persisted after excluding participants with preexisting immunocompromising conditions.
• In PASC symptom clusters, slight differences were noted:
  • Higher hsCRP levels in clusters 1 (smell/taste impairments) and 4 (multiple symptoms including fatigue and brain fog)
  • Lower sodium and higher calcium levels in cluster 2 (postexertional malaise and fatigue)
• The study suggests that routine laboratory tests are not useful biomarkers for PASC diagnosis.
• Clinicians should still use appropriate diagnostic testing to rule out treatable causes of PASC symptoms.
• The findings indicate that even highly symptomatic PASC may have no clinically observable objective findings on routine laboratory testing.
• Future research may need to focus on more advanced investigations (e.g., transcriptomics, proteomics, metabolomics) to identify novel biomarkers for PASC.

HCN Medical Memo
Although routine clinical laboratory tests do not provide reliable biomarkers for PASC, they remain important for ruling out other treatable causes of symptoms. Physicians should continue to use a comprehensive approach to diagnose and manage PASC, considering both patient-reported symptoms and objective clinical findings.

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