MMP-9, TIMP-9 in Lung Imaging and Functional of COVID-19
Condition: Pulmonary Infection; COVID-19; Extracellular Matrix Alteration
MeSH terms: COVID-19
Study type: Observational [Patient Registry]

Summary: 
      This study aims to determine the role of the extracellular matrix in lung abnormalities in
      COVID-19 patients. Anatomical abnormalities of the lungs can be observed by the presence of
      abnormalities on a chest x-ray that is scored using the Brixia index. The presence of
      COVID-19 pneumonia can impact oxygenation disorders. It is hoped that knowing the
      relationship between biomarkers that affect the extracellular matrix and anatomical and
      functional abnormalities can open up new insights into new therapeutic opportunities. The
      balance of MMP-9 and TIMP-1 has been studied in relation to several lung diseases other than
      COVID-19.
    

Detailed description: 
      Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2), which has different degrees of
      severity, is the cause of Coronavirus Disease 2019 (COVID-19). Over 97% of COVID-19 patients
      make a full recovery. Inflammation increases when COVID-19 severity increases. The lungs and
      endothelium will suffer harm when different pro-inflammatory cytokines are released. A
      cytokine storm is started when many immune cells produce cytokines and chemokines. The
      pro-inflammatory cytokine can increase angiogenesis, vascular permeability, keratin
      proliferation, and collagen production. Lung lesions are affected by certain disorders. In
      COVID-19 patients, angiogenesis, fibroblast activation, and collagen deposition all
      contribute to the repair of the lungs. The pathological outcome of acute or chronic
      interstitial pulmonary disease is lung fibrosis, characterized by abnormal collagen and
      extracellular matrix (ECM) deposition, the persistence of fibroblasts, failure of alveolar
      re-epithelization, and destruction of normal pulmonary architecture. The breakdown or buildup
      of ECM is influenced by the ratio of matrix metalloproteinase (MMP) and tissue inhibitor
      matrix metalloproteinase (TIMP). TIMP distribution, not MMP distribution, was the primary
      contributor to lung fibrosis. MMP expression is increased by the production of several
      hormones, cytokines (IL-1, IL-6), growth factors (TGF, TNF-), platelet-derived growth factor
      (PDGF), and basic fibroblast growth factor (bFGF).

      ECM assistance is required for the alveoli to function normally. Excessive ECM breakdown and
      aberrant ECM remodelling are the root causes of many respiratory conditions, including
      pulmonary fibrosis. ECM buildup destroys the alveolar process, particularly by impairing
      alveolar-capillary diffusion. On radiological images, lung abnormalities can be seen as
      pneumonia in the bilateral ground-glass opacity basal, which results in hypoxia. In the lower
      portion, bilateral abnormalities predominated. COVID-19 ARDS, hypoxemia, bilateral
      infiltrates, and reduced lung compliance were the hallmarks of pneumonia type H. Despite the
      limited sensitivity, plain chest X-rays can detect lung abnormalities in COVID-19; they are
      inexpensive and simple. New infiltrates on chest radiographs were used to make the diagnosis
      of pneumonia.

      Biomarkers of pulmonary interstitial abnormalities have received limited attention in the
      literature, including investigations on MMP and TIMP for lung abnormalities in COVID-19
      patients. One of the MMP gelatinase family's more complicated forms, MMP-9, can break down
      ECM components. MMP-9 increases collagen and cytokine production, fibroblast migration, and
      TGF- stimulation. MMP-9 is among the MMPs that TIMP1 effectively inhibits. TIMP-1 binds to
      pro- or latent MMP-9. For ECM proteolysis to occur, MMP and TIMP must coexist in equilibrium.
      This study aimed to ascertain how MMP-9 and TIMP-1 affected abnormal chest X-rays, poor
      oxygenation, severity, and death.

      Blood is taken from hospitalized COVID-19 patients to measure the serum concentrations of
      MMP-9 and TIMP-1. At the time of hospital admission, three reviewers assessed the severity
      after chest X-Rays, followed by a BRIXIA score. At the time of hospital discharge, patients
      were evaluated. The levels of MMP-9 and TIMP-1 were compared to Brixia scores, oxygen
      consumption, severity, and death.
    

Intervention name(s): MMP-9 and TIMP-1
Intervention type(s): Diagnostic Test
Intervention description(s): Examine level of serum MMP-9 and TIMP-1
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Adult hospitalized COVID-19 patients in Universitas Airlangga Surabaya, Indonesia, proven
        by positive swab RT-PCR COVID-19.
      
Biospecimen description: 
      A blood sample was taken from the sample study during admission (after the patient agreed to
      join the study and signed the informed consent). Blood is stored in a refrigerator at -80
      degrees Celsius. After all study samples have been collected, the blood is removed from the
      refrigerator and examined by ELISA. The distance between the first and last blood samples was
      about six months, and then a sample examination was carried out simultaneously. MMP-9 and
      TIMP-1 were checked using ELISA from sample blood.