COVID-19 Biomarkers

COVID-19 is characterised by a series of biological markers. In some instances, these biomarkers can be used as potential indicators of disease severity.

COVID-19 is the novel coronavirus disease caused by the viral agent SARS-CoV-2. With millions of confirmed cases across the world, the disease represents an unprecedented threat to public health. Additionally, the significant ramifications of an impacted healthcare system further broaden the danger that the virus presents. As the international community rushes to mitigate the economic and social damage the virus continues to cause, researchers seek to elucidate the mechanisms of the disease in hopes of finding effective prophylactic and therapeutic interventions.

Of particular interest is the role of the immune system— and more specifically, of immune dysregulation— in COVID-19. Cytokine Release Syndrome (CRS) in COVID-19 has garnered significant attention as a problematic development during the course of the disease. It is possible to test for CRS in patients who have confirmed infections or suspected infections.

Fig 1. Investigated biomarkers of SARS-CoV-2 infection (Adapted from GlobalData)

Recent data has shown an array of different proteins, cytokines, and cells which can be indicative of SARS-CoV-2 presence and COVID-19 severity. These markers could prove an important step in assessing the condition of a patient and thus inform possible treatment plans. A majority of the preliminary data has come from studies in China, where the virus originally emerged.

The compounds below have been identified in COVID-19.

The presence of the causative viral agent of COVID-19 is the strongest biomarker of infection. It is critical that these detection methods be both sensitive and specific, as there are many coronaviruses which have the potential to be present in humans. At the time of writing, several methods exist to test for the presence of SARS-CoV-2. These diagnostic measures include:

• Serological tests such as lateral flow immunoassays for patient-generated IgG and IgM antibodies
• RT-qPCR detection kits, including triplex-detection with multiple independent genes of SARS-CoV-2
• RNA can be extracted using specific kits and procedures
• Chest X-rays

Fig 2. SARS-CoV-2 viral particle representation

The cytokine IL-6 is unique among others of its kind. It possesses two paths of signal transduction via its receptor, and is a powerful mediator of inflammation. It is able to initialise signalling in a variety of cells, even if a cell type does not usually bear a transmembrane IL-6 receptor. IL-6 has been implicated as a key driver of cytokine release syndrome, and thus is a promising therapeutic target for severe cases of COVID-19 in which CRS is present.

Elevated levels of IL-6 can suggest that a patient is experiencing a dysregulated immune response to SARS-CoV-2 infection. Drugs such as Tocilizumab (Actemra®) reduce the potency of IL-6 and thus dampen its downstream effects. Tocilizumab is a humanised murine monoclonal antibody that targets the IL-6 receptor (both the soluble and membrane-bound variants). In 2017 it was approved for an additional indication: cytokine release syndrome.

Fig 3. CRP in its pentameric serum formation

CRP is an acute-phase protein synthesized in the liver. Its circulating concentration increases in response to inflammation, and it is considered a marker of an immune system response. Notably, CRP production is driven by IL-6 and other cytokines. CRP levels peak approximately 48 hours after the inciting event, but its short half life (19 hours in plasma) means it is cleared quickly from the body once triggers are removed.

CRP levels have been shown to correlate with lung lesion size and disease severity in COVID-19, according to one study in March of 2020.

Lymphocytes are cells of the immune system which function as coordinators and effectors. They include T cells, B cells, NK cells, and other cells derived from the common lymphoid progenitor cell type.

The differentiation and proliferation of lymphocytes is common in immune responses to infectious diseases. However, preliminary reports have suggested that lymphocyte levels may be altered, and specifically reduced, in patients with severe COVID-19. CD4+ T cells, and CD8+ T lymphocytes were shown to decrease in patients with more severe cases of SARS-CoV-2 infection.

Currently, trials are underway to evaluate more specific biomarkers. These include microRNAs, oxidative stress, IL-2, IL-6, TNF-alpha, leukocytes, and lymphocytes subtypes in COVID-19 positive patients versus control (COVID-19- negative) patients.

In addition to the biomarkers listed above, several other compounds have been found to be elevated in severe cases of COVID-19. These possible serum markers are listed below:

• Urea
• Creatinine
• Cystatin C (CysC)
• Cardiac troponin (hs-cTnI)
• B-type natriuretic peptide (BNP)
• N-terminal pro b-type natriuretic peptide (NT-proBNP)
• D-dimer
• ACE1 D/I polymorphism
• Platelet count
• Procalcitonin (PCT)
• Alanine aminotransferase (ALT)
• Lactate dehydrogenase (LDH)

For more information on the varying players of the immune system, see our Cells of the Immune System Collection.

• Macrophages
• Dendritic Cells
• Neutrophils
• B Lymphocytes