Biomarker of Post-COVID-19 Lung Fibrosis: A Systematic Review and Meta-Analysis of Cohort Studies

Gede Ari Mahendra Mardaningrat¹*, Putu Andrika², Isabella Soerjanto Putri¹, I Putu Hendri Aryadi¹

¹ Faculty of Medicine, Udayana University, Denpasar, Bali, Indonesia

² Division of Pulmonary and Critical Care, Department of Internal Medicine, Udayana University/Prof. dr. I.G.N.G Ngoerah Hospital, Denpasar, Bali, Indonesia

Abstract

Introduction: The World Health Organization (WHO) labeled COVID-19 as a pandemic. On January 7, 2024, an estimated 774,075,242 confirmed cases of COVID-19 had occurred, resulting in 7,012,986 deaths. Pulmonary fibrosis is commonly observed as a consequence of COVID-19 infection, with a reported prevalence of up to 83.3% in individuals who have recovered from the disease. Pulmonary fibrosis that develops after a COVID-19 infection arises from the immune system's reaction to the virus, resulting in inflammation and lung damage.

Objective: This systematic review and meta-analysis were conducted to determine the laboratory biomarker findings in patients with post-COVID-19 lung fibrosis.

Methods: Systematic review and meta-analysis adhering to the PRISMA and MOOSE guidelines. We conducted a literature search on PubMed, EMBASE, and Web of Science from January 1, 2020, to January 31, 2024.

Results: Nine eligible studies, including 1,406 patients, were identified. The research results showed that several biomarkers had statistically significant values such as lymphocytes (MD: -0.35; 95% CI: -0.49; -0.21), CRP (MD: 40.73; 95% CI: 27.78; 53.69), D-dimer (MD: 0.76; 95% CI: 0.18; 1.34), lactate (MD: 38.43; 95% CI: 19.73; 57.13), and interleukin-6 (MD: 16.97; 95% CI: 2.57; 31.37). Meanwhile, for biomarkers such as white blood cells (MD: 0.14; 95% CI: -0.54; 0.81) and neutrophils (MD: 3.71; 95% CI: -3.80; 11.23), the values were not statistically significant for the occurrence of lung fibrosis.

Conclusion: The diagnosis of pulmonary fibrosis is generally established using biopsy or CT scans. However, in some hospitals with limitations on healthcare resources and equipment such as CT scans, these biomarkers can be used in diagnosing pulmonary fibrosis, especially in patients after experiencing COVID-19 infection.

Keywords: Biomarker, COVID-19, Lung Fibrosis, Sars-Cov2