Lymphocytes are a type of white blood cell that play several roles in the immune system, including protection against bacteria, viruses, fungi, and parasites. Lymphocyte increased in response to infections or cancer. However, in covid-19 infection the lymphocyte decreased.
Lymphocytes are a type of white blood cell that play several roles in the immune system, including protection against bacteria, viruses, fungi, and parasites
The virus might directly infect lymphocytes, resulting in lymphocyte death. Lymphocytes express the coronavirus
The dynamic changes of lymphocyte subsets and cytokines profiles of patients with novel coronavirus disease (COVID-19) and their correlation with the disease severity remain unclear. Some of COVID-19 patients enrolled, severe cases showed significant and sustained decreases in lymphocyte counts but increases in neutrophil counts than mild cases. Further analysis demonstrated significant decreases in the counts of T cells, especially CD8 + T cells, as well as increases in IL-6, IL-10, IL-2 and IFN-γ levels in the peripheral blood in the severe cases compared to those in the mild cases. T cell counts and cytokine levels in severe COVID-19 patients who survived the disease gradually recovered at later time points to levels that were comparable to those of the mild cases. Moreover, the neutrophil-to-CD8+ T cell ratio (N8R) were identified as the most powerful prognostic factor affecting the prognosis for severe COVID-19.
The degree of lymphopenia and a proinflammatory cytokine storm is higher in severe COVID-19 patients than in mild cases, and is associated with the disease severity. N8R may serve as a useful prognostic factor for early identification of severe COVID-19 cases.
Hi Dr.Hasanain
Lymphocyte count has been associated with increased disease severity in COVID-19, Patients who died from COVID-19 are reported to have had significantly lower lymphocyte counts than survivors..
Extracorporeal membrane oxygenation (ECMO) can serve as life-saving rescue therapy for refractory respiratory failure in the setting of acute respiratory distress syndrome, such as that induced by coronavirus disease 2019 (COVID-19). During ECMO, substantial decreases in the number and function of some populations of lymphocytes is commonplace. As it might be hypothesised that repletion of lymphocytes could be key to recovery from COVID-19, lymphocyte count should be closely monitored in these patients receiving ECMO.
Good evening Dr. Hasanain
I think it is not the goal cell of the virus
Hi
Because Among the lymphocyte subgroups, B cell exhibited the most significant differences from the non-COVID-19-infected pneumonia patients. Since B cells are responsible for the humoral immunity against the invaders via producing antibodies[11] Another new and notable feature discovered is that the change in the proportion of the CD45+ lymphocytes was insignificant, compared with non-COVID-19 patients. This finding, first, demonstrates that the infection impacts on different lymphocyte subgroups evenly, and more interestingly, suggests that abnormality in cells that , the impotent response of B cells may fail to restrict the virus expansion and release of free virions in vivo, which promotes the infection.
Another new and notable feature discovered is that the change in the proportion of the CD45+ lymphocytes was insignificant, compared with non-COVID-19 patients. This finding, first, demonstrates that the infection impacts on different lymphocyte subgroups evenly, and more interestingly, suggests that abnormality in cells that regulate the adaptive immunity may be responsible for the reduction of lymphocytes. For instance, H5N1 infection causes lymphocytopenia through dendritic cell (DC) dysfunction [12] , suggesting the function of key antigen-presenting cells can be drastically impaired during the infection. According to a study in rats, the myeloid cells also express the COVID-19 receptor ACE2[13] Moreover, recent reports indicate that the infection can potentially damage other organs than the lung, including the kidney, heart, and the testis ; thus, we should consider the possibility of the virus infecting these cells, which is supported by the significant decrease in the platelet counts in both severe and non-severe COVID-19 patients.
Alveolar cells is important defense cells to destroy the virus so increase in compared with other leukocytes
Hi
It must be assumed that the novel corona virus interfere with the development of the lymphocytes at the hemopoetic centers of the body. Therefore, the overall number of lymphocytes in the blood circulation will be lower than its normal range.
Levels of lymphocytes and lymphocyte subsets are of great importance to keep the immune system functional. Usually viral infection, immunodeficiency diseases, and other infectious diseases lead to abnormal changes in the levels of lymphocyte subsets. At present, COVID19 is spreading over the world as a new clinical entity. Although a novel coronavirus has been identified as the cause of COVID19, we know little, as yet, about the mechanisms by which coronavirus impacts the human immune system
SARS-CoV-2 might mainly act on lymphocytes, especially T lymphocytes, and induce a cytokine storm in the body, generate a series of immune responses. Surveillance of NLR and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis and treatment of COVID-19
The dynamic changes of lymphocyte subsets and cytokines profiles of patients with novel coronavirus disease (COVID-19) and their correlation with the disease severity remain unclear. Some of COVID-19 patients enrolled, severe cases showed significant and sustained decreases in lymphocyte counts but increases in neutrophil counts than mild cases. Further analysis demonstrated significant decreases in the counts of T cells, especially CD8 + T cells, as well as increases in IL-6, IL-10, IL-2 and IFN-γ levels in the peripheral blood in the severe cases compared to those in the mild cases. T cell counts and cytokine levels in severe COVID-19 patients who survived the disease gradually recovered at later time points to levels that were comparable to those of the mild cases. Moreover, the neutrophil-to-CD8+ T cell ratio (N8R) were identified as the most powerful prognostic factor affecting the prognosis for severe COVID-19.
The degree of lymphopenia and a proinflammatory cytokine storm is higher in severe COVID-19 patients than in mild cases, and is associated with the disease severity. N8R may serve as a useful prognostic factor for early identification of severe COVID-19 cases.
https://www.medrxiv.org/content/10.1101/2020.02.19.20024885v1.full.pdf
The present study indicates significantly different clinical features between COVID-19-caused and non-COVID-19-caused pneumonia, especially in terms of lymphocytopenia and organ injury. Notably, correlation analysis demonstrates that tissue damage in COVID-19 patients is attributed to virus infection itself rather than uncontrolled inflammatory responses ("cytokine storm"). These findings provide new insights for developing efficient therapeutic strategies against COVID-19 infection.
dear sir
lymphocyte decrease because that virus induces the T lymphocyte apoptosis by activating intrinsic and extrinsic mechanism
Because of t.lymphocyte apoptosis is activated by intrinsic and extrinsic processes
https://www.medrxiv.org/content/10.1101/2020.02.19.20024885v1.full.pdf
because of excessive activation of mTORC1 due to coronavirus to replication and proliferation lead to decreases TSC1 regulatory pathway cause lymphopenia
this my review it might helps your inquiry
Azithromycin promising medicine for COVID 19 in early stage by effecting on mTOR and immune system
there are striking data in previous SARS and MERS studies, on these and other features, that may or may not apply to SARS Cov 2 (many still need to be proved for SARS Cov2)
The role of C5a in acute lung injury induced by highly pathogenic viral infections.
Decoding the enigma of antiviral crisis: Does one target molecule regulate all?
Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology : Article Pathogenic human coronavirus infections: causes and conseque...
all free now.
Cytokine storm triggered by the virus or necrosis as well as the virus avoiding Ab/immune system (conformational closed structure?) needs better elucidation. I would appreciate any info. thanks
file:///C:/Users/DrHasaneen/Downloads/Telegram%20Desktop/2020.02.19.20024885v1.full.pdf
Article Immune responses in COVID-19 and potential vaccines: Lessons...
Severe systemic inflammation causes T cells to undergo apoptosis. This is the natural equilibrium response by our body and immune system to prevent further amplification of pro-inflammatory responses by T cells which is very powerful. Just imagine if the host's system is already highly inflamed to a point it is about to kill the host, having a powerful pro-inflammatory T cell response ready to go and add on top of this highly inflamed environment is not a good idea in terms of natural selection.
This equilibrium response by T-cell apoptosis, however, comes at the cost of the host's capacity to the virus infection. But it at least allows the host to avoid and survive the more immediate danger systemic shocks and multi-organ failures as a result of the cytokine storms and buys the host some times to fight the virus infection by other means, e.g. antibody response.
What about lymphocyte sequestration into inflammed tissue. In this case the bigger the inflammed area in the lungs the lower lympocyte counts and correlation with risk of severity. proposed partially previously at: https://www.ijidonline.com/article/S1201-9712(05)00072-X/fulltext
See:
Giamarellos-Bourboulis EJ, Netea MG, Rovina N, Akinosoglou K, Antoniadou A, Antonakos N, Damoraki G, Gkavogianni T, Adami ME, Katsaounou P, Ntaganou M, Kyriakopoulou M, Dimopoulos G, Koutsodimitropoulos I, Velissaris D, Koufargyris P, Karageorgos A, Katrini K, Lekakis V, Lupse M, Kotsaki A, Renieris G, Theodoulou D, Panou V, Koukaki E, Koulouris N, Gogos C, Koutsoukou A.Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure.
Cell Host Microbe. 2020 Apr 17. pii: S1931-3128(20)30236-5. doi: 10.1016/j.chom.2020.04.009. [Epub ahead of print]
Secretion of cytokines and chemokines attracts immune cells, notably monocytes and T lymphocytes, but not neutrophils, from the blood into the infected site. Pulmonary recruitment of immune cells from the blood and the infiltration of lymphocytes into the airways may explain the lymphopenia and increased neutrophil–lymphocyte ratio seen in around 80% of patients with SARS-CoV-2 infection.
https://www.nature.com/articles/s41392-020-0148-4#ref-CR6
"We speculated four potential mechanisms leading to lymphocyte deficiency. (1) The virus might directly infect lymphocytes, resulting in lymphocyte death. Lymphocytes express the coronavirus receptor ACE2 and may be a direct target of viruses.5 (2) The virus might directly destroy lymphatic organs. Acute lymphocyte decline might be related to lymphocytic dysfunction, and the direct damage of novel coronavirus virus to organs such as thymus and spleen cannot be ruled out. This hypothesis needs to be confirmed by pathological dissection in the future. (3) Inflammatory cytokines continued to be disordered, perhaps leading to lymphocyte apoptosis. Basic researches confirmed that tumour necrosis factor (TNF)α, interleukin (IL)-6, and other pro-inflammatory cytokines could induce lymphocyte deficiency.6 (4) Inhibition of lymphocytes by metabolic molecules produced by metabolic disorders, such as hyperlactic acidemia. The severe type of COVID-19 patients had elevated blood lactic acid levels, which might suppress the proliferation of lymphocytes"
The observation of severe lymphopenia in severe and critical cases of Covid19 patients are probably a reflection and indication of a systematic hyper-activated state of circulating T cells and severe inflammation due to cytokine storm. Similar observations of T cell lymphopenia and T cell exhaustion are seen in human sepsis and clinical trial of anti-CD28 superagonist case in 2006.
https://www.ijidonline.com/article/S1201-9712(05)00072-X/fulltext
body’s potent immune response to COVID-19 poses unique risks to the heart, but as accumulating data suggest, this opens the door to a host of anti-inflammatory agents as potential therapies, many of them having already been tested in the prevention of cardiovascular events.
Researchers around the world are hoping that this link, especially as it relates to interleukin-6 (IL-6) and its precursor interleukin-1 (IL-1), will provide new ways to temper symptoms and reduce complications in patients suffering a severe course of this deadly disease.
“Whereas COVID-19 is primarily a respiratory infection, it has important systemic effects including on the cardiovascular and immune systems. Patients with preexisting cardiovascular conditions represent large proportions of patients with symptomatic infection, and experience disproportionately worse outcomes at between five- to tenfold increase in mortality,” Peter P. Liu, MD (University of Ottawa, Canada), and colleagues note in a review of the topic recently published in Circulation.
Systemic inflammation has long been posited as a trigger for cardiovascular events. Here, in the setting of COVID-19, many believe anti-inflammatory agents have an important role to play in bringing the virus to heel.
“We believe that, in part, one of the relevant pathways involved in the inflammatory storm, the so-called cytokine storm, associated with COVID-19 is the IL-1/IL-6 pathway, . . . which is also very relevant in cardiovascular disease,” Jean-Claude Tardif, MD (Montreal Heart Institute, Canada), told TCTMD. Tardif led last year’s COLCOT trial showing that colchicine can reduce ischemic events post-MI.
https://www.tctmd.com/news/hopes-high-anti-inflammatories-combat-covid-19-immune-system-storms
LYM% indicates disease severity of COVID-19 patients
The classification of disease severity in COVID-19 is very important for the grading treatment of patients. In particular, when the outbreak of an epidemic occurs and medical resources are relatively scarce, it is necessary to conduct grading severity and treatment, thereby optimize the allocation of rescue resources and prevent the occurrence of overtreatment or undertreatment. According to the latest 5th edition of the national treatment guideline, COVID-19 can be classified into four types. Pulmonary imaging is the main basis of classification, and other auxiliary examinations are used to distinguish the severity. Blood tests are easy, fast, and cost-effective. However, none of the indicators in blood tests were included in the classification criteria. This study suggested that LYM% can be used as a reliable indicator to classify the moderate, severe, and critical ill types independent of any other auxiliary indicators.
Analysis of possible reasons for lymphopenia in COVID-19 patients
Lymphocytes play a decisive role in maintaining immune homeostasis and inflammatory response throughout the body. Understanding the mechanism of reduced blood lymphocyte levels is expected to provide an effective strategy for the treatment of COVID-19. We speculated four potential mechanisms leading to lymphocyte deficiency. (1) The virus might directly infect lymphocytes, resulting in lymphocyte death. Lymphocytes express the coronavirus receptor ACE2 and may be a direct target of viruses.5
(2) The virus might directly destroy lymphatic organs. Acute lymphocyte decline might be related to lymphocytic dysfunction, and the direct damage of novel coronavirus virus to organs such as thymus and spleen cannot be ruled out. This hypothesis needs to be confirmed by pathological dissection in the future. (3) Inflammatory cytokines continued to be disordered, perhaps leading to lymphocyte apoptosis. Basic researches confirmed that tumour necrosis factor (TNF)α, interleukin (IL)-6, and other pro-inflammatory cytokines could induce lymphocyte deficiency.6
(4) Inhibition of lymphocytes by metabolic molecules produced by metabolic disorders, such as hyperlactic acidemia. The severe type of COVID-19 patients had elevated blood lactic acid levels, which might suppress the proliferation of lymphocytes.7 Multiple mechanisms mentioned above or beyond might work together to cause lymphopenia, and further research is needed.
Study of the lymphocyte change between COVID-19 and non-COVID-19 pneumonia cases suggesting other factors besides uncontrolled inflammation contributed to multi-organ injury
The lymphopenia has been found to be a poor prognostic marker.
It is not a universal phenomenon.
The experience of stable covid patients and their lymphocyte count will shed better light.
In our tertiary care centre, lymphopenia in stable patients was infrequent.
To Samah Ahmed Kadhum Al-jebory Can you please add the attribution to your popular answer. Most of it is copied word-for-word, unattributed, from
https://www.medrxiv.org/content/10.1101/2020.02.16.20023671v2.full.pdf
Thank you.
Is there any evidence of lymphocytosis in literature in very mild COVID probably an adequate/ better than normal response by the immune system. I ask this since I see a lot of patients with a viral like illness in the Covid epidemic where they are febrile only for a couple of days, becoming asymptomatic thereafter, and cbc shows lymphocytosis around 50% with 10% monocytes but with a mild leukopenia around 3500/cmm. Usually do not end up doing PCR since patient becomes asymptomatic by third or fourth day. It is an Infectious Mononucleosis like picture but can't explain how so many patients can suddenly start having IM in a COVID pandemic and that too in all age groups. Please comment.
You might check this out, Article Reduction and Functional Exhaustion of T Cells in Patients W...
there is a fair amount of literature on the subject.
Dr Zubin,
We have found relative lymphocytosis with leukopenia in the asymptomatic and mild covid patients.
Though the number of such patients at present is small.
Literature for lymphopenia in sick patients is robust, but vice versa evidence is lacking at present
Our small initial data which has been consistent till a month back.
However, now as cases are mounting each day, such mild or stable patients are no longer admitted in our tertiary care cente as per national guidelines
https://www.researchgate.net/publication/342096774_Relative_lymphocytosis_in_COVID-19_-a_ray_of_hope_Ahead_of_print
As a acute infection , there is changing of leucocyte differention besides of maturation , because of inflammatory cytokines released particularly TNF, and IL-1. Thus increase neutrophils and decrease lymphocytes as a consequences. But in severe Covid infection with inflammatory cytokines storms, the leucocyte differentions changing are remarkable
Dianiati Kusumo Sutoyo
As I’m sure you’re aware, there are reports of covid-19 patients having low neutrophil to lymphocyte ratios (NLR) being at lower risk of developing critical illness from covid-19, and it has been suggested a low NLR could be used as a predictor (refs below).
Would you have a view on whether as-yet uninfected patients bordering on neutropenia (~ 2x10^9/L) with normal lymphocyte count (2.2x10(/L), and therefore a low NLR prior to a possible infection, would be at low risk if they subsequently become infected, or is it only shortly after infection that the NLR would be predictive?
If predictive prior to infection this could be especially helpful in care-home settings of the elderly.
Some of the graphs, copied into the attached .docx file from the end of: https://www.medrxiv.org/content/10.1101/2020.02.16.20023671v2.full.pdf
show selected blood counts from day-3 of infected patients, and might, perhaps, be interpreted as suggesting that the “Mild patients” had a low NLR prior to infection?
I would value your opinion.
Best regards – Paul G. Ellis
20 May 2020 https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02374-0
“Results The neutrophil-to-lymphocyte ratio (NLR) was identified as an independent risk factor for critical illness in patients with COVID-19 infection. The NLR had an area under receiver operating characteristic of 0.849 (95% confidence interval [CI], 0.707 to 0.991) in the derivation cohort and 0.867 (95% CI 0.747 to 0.944) in the validation cohort, the calibration curves fitted well, and the decision and clinical impact curves showed that the NLR had high standardized net benefit. In addition, the incidence of critical illness was 9.1% (1/11) for patients aged ≥ 50 and having an NLR
First because the lymphocytes migrate to the tissues and also cytokine storm causes lymphocytes to start apoptosis.