Any viral infection leads to a decrease in lymphocyte levels but the change varies from virus to virus. In the case of COVID-19, it has been found out that CD8+ cells (Cytotoxic T cells) play an important role in predicting the severity of the infection and therefore are crucial in designing a proper treatment method. It has been observed that the levels of CD4+ and CD8+ cells decrease drastically in severe cases but not so much in milder ones. Even though a change in CD4+ to CD8+ ratio is not seen. It was observed that the CD4+ and CD8+ levels start rising as the body responds to treatment. 

Effect of COVID-19 on T-cell levels in infected patients

T-cells play a huge role in cellular immunity of the body, by injecting toxic substances in the pathogen to kill it. A COVID-19 infection can lead to decreased T-cell levels. New studies suggest that a unique structure on the COVID-19 spike protein fuses with the T-cell when the two get in contact, thereby disrupting its natural function. The virus upon entering the T-cell prevents it from performing its phagocytic function and can lead to decreased immunity. 

Mechanism of viral attack on T-cells

Studies show the activation of a different kind of T-cell called MAIT cell, which is an anti-bacterial cell but can also fight against certain viruses. These MAIT cells are seen to be strongly activated in the people who suffer from severe COVID-19, their number also seems to be declining indicating to the fact that they are involved in the fight against the virus. They are also seen to accumulate in the airways of the patient to a greater extent than a normal healthy person. 

Strong activation of antibacterial T cells or MAIT cells in severe COVID-19

- CD4+ T cell responses are more responsible for controlling SARS-CoV-2 infection than CD8+ T cells
- induction of antibodies also depend on spike-specific CD4+ T cells
- in a study examining CD4+ T cell responses to all SARS-CoV-2 proteins, CD4+ T cell responses were detectable for all but three of the smallest proteins
- S spike protein, M, and nucleocapsid were the main targets of CD4+ T cells
- virus specific CD4+ T cells differentiate into Th1 cells and T follicular helper cells (Tfh)

CD4+ T cell response in SARS-CoV-2 infection

- presence of SARS-CoV-2 specific CD8+ T cells has been associated with better COVID-19 outcomes
- CD8+ T cells are specific for a range of SRS-CoV-2 antigens including S spike protein, M, nucleocapsid and ORF3a
- in acute COVID-19, SARS-CoV-2 specific CD8+ T cells exhibit high levels of association with effector functions such as IFNy, granzyme B, perforin, and CD107a

CD8+ T cell response in SARS-CoV-2 infection

- CD8+ T-cells: Directly attacks and kills virus-infected cells
- CD4+ T-cells: Primes CD8+ T cells and antibody-producing B cells, responsible for cytokine production
- T-cell exhaustion and reduced functional diversity lead to severe disease

University of California, Davis

Michigan State University

Smith College

A review study presented on the pathophysiology of the COVID-19 virus and found that entry and replication by the virus into cells expressing ACE 2 receptors triggers host cell pyroptosis, generating pro-inflammatory cytokines and chemokines which recruit monocytes, macrophages, and T-cells. This results in further inflammation and creation of a pro-inflammatory feedback loop, leading to overproduction of cytokines that accumulate in the lungs, causing a cytokine storm.

Review Investigating the Immunopathogenesis of COVID-19

- B-Cell Immunity in COVID-19
- T-Cell Immunity in COVID-19
Adaptive response process
- Blood brings the cells throughout the body as normal where the B cells are working alongside t cells to go into the plasma where they produce antibodies specific to the antigen.  
- A neutralizing antibody is efficient in fully blocking the virus from entering the host cells. This helps limit the infection and relapse. 
- The overall adaptive immune response is directed by helper T cells, and cytotoxic T cells play a vital role in the clearance and cleaning of viral-infected cells
- Adaptive immune response against coronavirus requires stimulation of B cell and T cell epitopes


Adaptive Immune Response to COVID-19

Tay, M. Z., Poh, C. M., Rénia, L., Macary, P. A., &amp; Ng, L. F. (2020). The trinity of COVID-19: Immunity, inflammation and intervention. Nature Reviews Immunology, 20(6), 363-374. doi:10.1038/s41577-020-0311-8
https://www.nature.com/articles/s41577-020-0311-8

The trinity of COVID-19: immunity, inflammation and intervention

Figure: Chronology of events during SARS-CoV-2 infection.

- Response occurs ~1 week after onset of symptoms
- Some may not develop long-lasting antibodies to the virus
- Convalescent plasma treatment is a viable option
- The majority of antibodies to SARS-CoV-1 do not bind to the SARS-CoV-2 virus, likely due to differences in the receptor-binding-domain

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