What Is COVID-19?
The Coronavirus disease (COVID-19), known to be caused by a novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) hit the world in 2019. The first case was found to be in Wuhan in China in December 2019, followed by which the virus spread all over the world. COVID-19 is rapidly spreading as a devastating global pandemic.
Now after the third wave has hit the world, it is firmly believed that COVID-19 will only increase, and so would be the increasing demand for intensive care. In such a scenario, the identification of critical patients plays a vital role in the better management of the disease.
What Is the Significance of Lymphocyte Count in COVID-19?
Studies done from the data obtained from the severe forms of the disease of Middle East respiratory syndrome coronavirus and recent studies concerning SARS-CoV-2 show that the response of the immunity of the host is a major contributory key factor to the pathogenesis of COVID-19. It revealed that cytotoxic T lymphocytes and natural killer cells play a key role in the control of viral infection.
Exhaustion of the antiviral type of lymphocytes is reportedly seen in patients with COVID-19. However, there is still very little evidence available for concluding the importance of lymphocyte count in predicting the severity of COVID-19.
The increase in the ratio of monocyte: lymphocyte and neutrophil: lymphocyte, and peaks of cytokines, like interleukin-2R, correlated with the severity of the disease and poor outcomes. Although the pathophysiology involved in COVID-19 has not yet been clearly known, recent studies have helped to understand the underlying mechanisms responsible for the observed lymphopenia, which would be helpful for understanding the disease pathogenesis and would help in better management of such patients.
The role of antibodies in the process of recovery of COVID-19 patients is fully understood. At the same time, it is also believed that the key to recovery is not only the B cell activity. A patient of COVID-19 with multiple sclerosis, treated with an anti-CD20 B cell depleting antibody (Ocrelizumab), fully recovered after hospitalization for a few days. A similar study showed a COVID-19 patient having X-linked agammaglobulinemia (XLA), which is amongst very less frequently seen genetic disorders resulting in almost no mature B cells but had a good outcome showing complete resolution. Pneumonia was developed in this patient but resolved without mechanical ventilation or intensive care.
Such cases have brought into the limelight the importance of B cells in the resolution of disease in SARS-CoV-2 infection. Another study revealed that antibody-secreting cells are higher in number in severe cases of COVID-19 compared to that in milder ones. Numerous studies have shown that titers of virus-specific antibodies are directly proportional to the severity of the disease.
The fact that these antibodies are protective or not still remains unclear because studies on similar viruses have also shown two types of antibody response; one being neutralizing and protective, whereas another that can exacerbate inflammatory responses and can cause lung injury. However, further studies are required to clearly understand the significance of increased antibody titers in the severity of the disease of COVID-19.
What Is the Possible Cause of Decreased Lymphocyte Counts in COVID-19 Patients?
In this article, we hypothetically state the decrease in T-cell counts as the most important cause of lymphopenia in severe COVID-19 patients. The inflammatory cytokine storm plays a vital role in lymphopenia seen in COVID-19 patients. Proinflammatory cytokines levels like TNF-α (tumor necrosis factor-alpha) and IL-6 f(interleukin -6) relate directly to lymphopenia, whereas normal levels of such cytokines are seen in patients who have recovered.
Autopsy-based studies done on patients’ lymphoid organs who died due to COVID-19 showed rapid death of lymphocytes, which was found to be due to increased levels of IL-6 and Fas-FasL interactions. After treatment with Tocilizumab, an IL-6 receptor antagonist, circulatory lymphocytes increased in number, which suggested that raised IL-6 is the most important factor for lymphopenia. There has been another study suggesting a vital correlation between the levels of IL-6 in patients affected with coronavirus and the impairment of the cytotoxic activity of T cells and NK (natural killer) cells. COVID-19 shows a rapid decrease in T cells.
Another study revealed an increase in the amount of cell surface expression of T cell immunoglobulins, programmed cell death protein 1 (PD-1), and mucin domain 3 (Tim-3) in CD4+ and CD8+ T cells of Covid-19 patients. Thus the severity of the disease directly correlated to PD-1 and Tim-3. Thus, the severity of the disease did not affect the regulatory T cell number, which suggests that T cell depletion can occur unrelated to regulatory T cells. Therefore, further studies are still needed for more understanding of the relationship between the exhaustion of T cells and SARS-CoV-2 infection.
COVID-19 has the potential to cause T-cell infection. Studies have shown that human cell lines can be infected with the virus present in vitro despite having very low levels of human ACE2 mRNA, the receptor through which it enters the host. However, as evaluated by qPCR (polymerase chain reaction) expression of the viral N gene, the virus does not have the potential to reproduce within infected cells. At the same time, a different study revealed that there was a lack of expression of the viral gene in patients with COVID-19, which suggests that there was no infection of the lymphocytes. This demands more research for a better understanding of the fact that there can be direct or indirect infection of any immune cell subsets.
The SARS-CoV-2 virus is said to be involved with the expansion of T cells. A report suggested downregulation in the genes responsible for T cell activation and function, such as SOS1 and MAP2K7, in the case of COVID-19. Most of these genes are usually normal at the time of recovery. This is probably because of the tremendous variation in the milieu of the cytokines in due course of infection.
Decreased lymphocyte count is a notable part of severe COVID19. The raised level of certain cytokines, like IL-6, and a marked decrease in lymphocytes are directly proportional to the disease severity. In severe cases, a noticeable reduction in T cell count is seen. Also, it is suggestive of the fact that immunosuppressive agents like Th1 (helper T) cells, which are responsible for suppressing T cell response, may be deleterious to fight against COVID-19 and hence not recommended in premorbid patients having autoimmune diseases.
More detailed studies are required in order to emphasize the pattern of lymphocyte changes in patients with COVID-19 in order to confirm and comment on the definitive role of lymphocytes as a predictor of severity in COVID-19 patients.