Since 1700, the researchers were very fond of understanding the body’s defence mechanism against any foreign particle entering our body. When they started understanding the immune system they found that immune response is just like the soldiers at the country border to protect the country from enemies. Similarly, our body also has guards (cells) which protect our body from foreign particles like virus , bacteria , fungi(fig 1).The cells are mainly present in the blood and are known as white blood cells (leucocytes) which include neutrophils , lymphocytes , monocytes(macrophages) , eosinophils , basophils.

Immune cells guarding our body like soldiers when there is an entry of virus

After the COVID19 outbreak in Wuhan (China) 2019, researchers became keen to know the immune response toward this contagious coronavirus. The clinical infectious disease journal published  a research article, which tried to study the manipulation of immune response by COVID-19 and how it can be used for early diagnosis. In this report we are going to understand how the researchers studied the immune response against COVID19.



The lymphocytes are the key players in the immune system which are divided based on the functions they perform:

  • T Helper Lymphocyte: They are the main cells of our immune system as they activate and proliferate all other cells involved in an immune response. It is denoted as CD4+, as it contains this protein at the membrane, which acts as a marker.
  • T Cytotoxic Lymphocyte: It mainly helps in killing virus infected cells and tumor cells, and it is activated by T helper cells. It contains marker CD8+ proteins in cell membrane.
  • T Regulatory Lymphocyte: It helps in deactivating and regulating activated immune response when the immune response become hyper active.
  • B Lymphocyte: Is activated by helper T cells and produce antibodies against specific antigens when activated.

So, lymphocyte subset count is a very important parameter to know whether immune system is functioning properly or not.


Whenever there is an entry of a foreign particle at any tissue the cells need to communicate with each other, so they produce certain proteins called cytokines, which help them to know that there is an infection at some part of the body. The first cells which come to rescue are the macrophages present at the site of infection, release cytokines (TNF-α, IL-1 and IL-6) which act as a magnet and attract immune cells (neutrophils, lymphocytes, etc) present in the nearest blood vesselThere are also certain cells called mast cells that release certain chemicals like histamine, this along with cytokines helps in forming pore in the nearest blood vessel and also widens it, so that leucocytes residing in the bloodstream can migrate to the infected tissue. Thus, Th1 cells get activated which in turn releases cytokines that activate more macrophages and hence it forms a loop that lead to a phenomenon called CYTOKINE STORM. (Fig 2)

Cytokine storm comparison
Illustration of how a cytokine storm may look like high waves in a sea.

When the infection is prolonged the cytokines then travel to different organs which lead to production of more cytokines, this situation is known as systemic inflammation. The cytokine storm can cause various organ failure and thus need to be regulate by T regulatory cells.


  • The molecules which help in identifying diseased condition of the body are known as biomarkers


These are some examples of acute phase protein whose concentration increase whenever there is an immune response (inflammation).When there is a systemic inflammation the cytokine from the site of injury travels to liver directly or indirectly through brain and adrenal gland, this lead to expression of these acute phase proteins.(Fig 3)These proteins in turn activate complement proteins which are another type of proteins produced by liver and thus complement proteins activate a cascade of reaction which attacks the foreign particle (virus ,bacteria ,etc) and causes lysis of the cell.

Production of ACP
Flow chart representing cytokine travelling to different organs and helping to produce acute phase


Neutrophils which are the most  abundant leucocytes(WBC) present in the blood and arrive first at the site of infection after the macrophage release cytokines plays as both hero an villain for the body. Whenever there is any bacterial , viral , fungal infection neutrophils play a crucial role in protecting our body, but it was seen by some researchers that in viral infection whenever there is a prolonged activation of neutrophils it lead to pneumonia or respiratory distress. In some cases it was seen that neutrophils recruited to the lungs of infected persons produce proinflammatory cytokines which may lead to hyper activated immune response .When the lymphocyte number decreases in comparison to neutrophils it is used as a biomarker as an indication of disregulation of immune response.

Researchers grouped patients into severe and non-severe

In severe patients it was seen that: 

  1. Low T helper lymphocyte and T regulatory lymphocyte. (lymphopenia).
  2. High NLR
  3. Higher age and patients with any added disorder like diabetes were affected more.
  4. High cytokines (TNF-α, IL-1 and IL-6) and chemokines (IL-8).


  • Based on these results, they suggested that COVID-19 might damage lymphocytes, especially T lymphocytes, and the immune system was impaired during the period of disease.
  • Increased NLR can be used for earlier diagnosis.
  • More percentages of cases underlying disorder (i.e., hypertension, diabetes, chronic obstructive pulmonary disease) was seen, and a higher percentage of hypertension and cardiovascular disease in the severe cases.
  • Age of the patient also plays an important factor as the immune system weakens as age exceeds.
  • High cytokine levels suggested that there was systemic inflammation involved due to low T regulatory lymphocyte cells.

“Thus, COVID-19 may be successful in manipulating our immune system which can be a serious threat in future and also earlier diagnosis is a very crucial area so learning about NLR as a biomarker is one of the important steps”


INFLAMMATION: Whenever there is an entry of any foreign substance the first defence of immune system  leads to an inflammation which is a part of innate immune system( not acquired during lifetime).Inflammation is a sign of activation of immune system.The signs of inflammation are pain,generation heat,redness,swelling.

PROCALCITONIN : It is a protein precursor of calcitonin which is secreted by C cells of thyroid and neuroendocrine cells of lungs and intestine, it is used as biomarker for diagnosis as its concentration varies when there is a microbial infection, so it is categorised as acute phase reactant.

LYMPHOPENIA : When there is abnormally low level of lymphovytes in the blood, such condition is termed as lymphopenia. It is mainly seen in viral infected patients.


Qin, C., Zhou, L., Hu, Z., Zhang, S., Yang, S., Tao, Y., Xie, C., Ma, K., Shang, K., Wang, W. and Tian, D.S., 2020. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clinical Infectious Diseases.

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