Inflammatory and vascular biomarkers in post-COVID-19 syndrome: A systematic review and meta-analysis of over 20 biomarkers

Yong SJ 1 , Halim A 2 , Halim M 3 , Liu S 4 , Aljeldah M 5 , Al Shammari BR 5 Show all authors , Alwarthan S 6 , Alhajri M 6 , Alawfi A 7 , Alshengeti A 7 , Khamis F 8 , Alsalman J 9 , Alshukairi AN 10 , Abukhamis NA 11 , Almaghrabi FS 11 , Almuthree SA 12 , Alsulaiman AM 13 , Alshehail BM 14 , Alfaraj AH 15 , Alhawaj SA 16 , Mohapatra RK 17 , Rabaan AA 18

Affiliations 

  • 1 Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Selangor, Malaysia
  • 2 Shanghai Medical College, Fudan University, Shanghai, China
  • 3 Department of Biomedical Science, School of Science, Engineering and Environment, University of Salford, Greater Manchester, UK
  • 4 Centre for Surveillance and Applied Research, Public Health Agency of Canada, Ottawa, Ontario, Canada
  • 5 Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Hafr Al Batin, Hafr Al Batin, Saudi Arabia
  • 6 Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
  • 7 Department of Pediatrics, College of Medicine, Taibah University, Al-Madinah, Saudi Arabia
  • 8 Infection Diseases Unit, Department of Internal Medicine, Royal Hospital, Muscat, Oman
  • 9 Infection Disease Unit, Department of Internal Medicine, Salmaniya Medical Complex, Ministry of Health, Manama, Bahrain
  • 10 Department of Medicine, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi
  • 11 Molecular Virology Laboratory, East Jeddah Hospital, Jeddah, Saudi Arabia
  • 12 Department of Infectious Disease, King Abdullah Medical City, Makkah, Saudi Arabia
  • 13 Laboratory Department, Almostaqbal Medical Laboratories, Riyadh, Saudi Arabia
  • 14 Pharmacy Practice Department, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
  • 15 Pediatric Department, Abqaiq General Hospital, First Eastern Health Cluster, Abqaiq, Saudi Arabia
  • 16 Department of Nursing Model of Care, Nephrology Dialysis & Transplant Unit, Qatif Central Hospital, Qatif, Saudi Arabia
  • 17 Department of Chemistry, Government College of Engineering, Keonjhar, India
  • 18 College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
Rev Med Virol, 2023 Mar;33(2):e2424.
PMID: 36708022 DOI: 10.1002/rmv.2424

Abstract

Severe acute respiratory syndrome coronavirus 2 may inflict a post-viral condition known as post-COVID-19 syndrome (PCS) or long-COVID. Studies measuring levels of inflammatory and vascular biomarkers in blood, serum, or plasma of COVID-19 survivors with PCS versus non-PCS controls have produced mixed findings. Our review sought to meta-analyse those studies. A systematic literature search was performed across five databases until 25 June 2022, with an updated search on 1 November 2022. Data analyses were performed with Review Manager and R Studio statistical software. Twenty-four biomarkers from 23 studies were meta-analysed. Higher levels of C-reactive protein (Standardized mean difference (SMD) = 0.20; 95% CI: 0.02-0.39), D-dimer (SMD = 0.27; 95% CI: 0.09-0.46), lactate dehydrogenase (SMD = 0.30; 95% CI: 0.05-0.54), and leukocytes (SMD = 0.34; 95% CI: 0.02-0.66) were found in COVID-19 survivors with PCS than in those without PCS. After sensitivity analyses, lymphocytes (SMD = 0.30; 95% CI: 0.12-0.48) and interleukin-6 (SMD = 0.30; 95% CI: 0.12-0.49) were also significantly higher in PCS than non-PCS cases. No significant differences were noted in the remaining biomarkers investigated (e.g., ferritin, platelets, troponin, and fibrinogen). Subgroup analyses suggested the biomarker changes were mainly driven by PCS cases diagnosed via manifestation of organ abnormalities rather than symptomatic persistence, as well as PCS cases with duration of <6 than ≥6 months. In conclusion, our review pinpointed certain inflammatory and vascular biomarkers associated with PCS, which may shed light on potential new approaches to understanding, diagnosing, and treating PCS.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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