Stroke Patients: Immunocompromised Or Not?

Stroke patients are at an increased risk of developing severe COVID-19, likely due to stroke-induced alterations to their systemic immune function.

Infection is a common complication of stroke, occurring in up to one-third of patients. Bacterial infections affecting mucosal surfaces such as the uro-genital and respiratory tracts are the most prevalent, and pneumonia, in particular, has been independently associated with increased short- and long-term morbidity and mortality.

The suppression of systemic immunity is reported to begin within 12 hours after stroke and can persist for weeks to months. This suppression includes reduced abilities to produce pro-inflammatory cytokines and effectively present antigens, which might result in a dampened anti-viral response.

In addition, a number of the immune alterations induced by stroke are also reported in severe COVID-19, including innate immune cell deficiencies, lymphopenia, and TH2-skewing. Therefore, the immunological profile of people recovering from stroke might compound many of the deleterious immune factors elicited by COVID-19.

Stroke patients are at an increased risk of severe COVID-19 due to the immunosuppression that follows stroke

Stroke patients are at an increased risk of severe COVID-19 due to the immunosuppression that follows a stroke. The immune system is broadly divided into innate and adaptive arms, both of which play a crucial role in protecting against and clearing infections. The immune response to SARS-CoV-2 is critical in preventing severe disease, and a timely and robust immune response is required to avoid it. However, a stroke can suppress the immune system, making it less able to fight infections. This suppression can begin within 12 hours of a stroke and last for several months.

The innate immune system is the body's first line of defence against infections. Stroke patients often experience functional deficiencies in various innate immune cells, such as monocytes, macrophages, and natural killer (NK) cells. These cells are critical for destroying infected cells and presenting antigens to the adaptive immune system. After a stroke, these cells may produce fewer pro-inflammatory cytokines and display reduced expression of HLA-DR, which is required for antigen presentation. Similar deficiencies in the innate immune system are observed in COVID-19 patients, indicating a potential overlap in immune dysfunction between the two conditions.

The adaptive immune system, composed of B and T cells, is equally important in the anti-viral response. Stroke patients experience lymphopenia, or a loss of lymphocytes, which includes a reduction in B and T cells. This loss of lymphocytes is also observed in severe COVID-19 cases and is associated with increased disease severity. Additionally, stroke patients exhibit a shift from a pro-inflammatory TH1 response to an anti-inflammatory TH2 response, which may foster tissue repair but also increases susceptibility to infections. This shift is characterised by reduced levels of interferon-gamma (IFN-γ) and increased levels of interleukin-10 (IL-10). A TH2-dominated response is also associated with more severe COVID-19.

The combination of immunosuppression following a stroke and the immune system's response to COVID-19 may result in a compounding effect that increases the risk of severe COVID-19 in stroke patients. The extent and duration of immune deficits after a stroke are not yet fully understood, and further studies are needed to determine the specific risk factors and develop effective treatment strategies for this vulnerable patient group.

Stroke patients are more likely to develop severe COVID-19 due to the overlap of immune alterations induced by stroke and COVID-19

Stroke patients are at an increased risk of developing severe COVID-19, which is likely due to the changes in their immune system post-stroke. These changes include a suppression of the immune system, which can persist for weeks to months. This suppression includes a reduction in the ability of monocytes and macrophages to produce pro-inflammatory cytokines, defective NK cells, and a reduction in the number of lymphocytes.

COVID-19, similarly, induces changes in the immune system, including the loss of lymphocytes, which is associated with more severe COVID-19. The loss of lymphocytes is extensive, with the spleens and lymph nodes of those who succumbed to COVID-19 reported to harbour one-third the number of T and B cells compared to individuals who died from non-COVID-19-related causes. In addition, there is a shift from a TH1 (IFNγ) to TH2 (IL-4, IL-10) phenotype, which is thought to foster tissue repair and protect against additional brain injury but contributes to infection vulnerability in patients.

The immunosuppression that follows a stroke, therefore, may compound and exacerbate the immunopathology induced by SARS-CoV-2 infection. This overlap of immune alterations induced by stroke and COVID-19 may result in a compounding effect that contributes to worsened disease severity.

The immunosuppression that follows stroke may preclude or delay the generation of a potent anti-viral response, thus rendering people with a history of stroke more likely to develop severe disease

The Immunosuppression That Follows Stroke and Its Impact on COVID-19

Stroke patients are at an increased risk of developing severe COVID-19, likely due to stroke-induced alterations to their systemic immune function. The immunosuppression that follows a stroke may delay or prevent the generation of a potent anti-viral response, thus rendering those with a history of stroke more likely to develop severe disease.

Immunosuppression After a Stroke

Following a stroke, a suppression of the systemic immune function can occur, which may protect the brain from incurring further damage as a consequence of over-activation of inflammatory pathways. However, this suppression also reduces the body's defences against infection. This suppression of the immune system is reported to begin within 12 hours of a stroke and can persist for weeks to months.

The Impact of Immunosuppression on COVID-19

The immune response to SARS-CoV-2 relies on coordination by various components of the immune system, including both the innate and adaptive arms. However, a number of the peripheral immune factors that contribute to the anti-viral response are suppressed following a stroke. For example, pro-inflammatory cytokines are downregulated, and multiple immune cell populations display functional deficiencies.

Overlapping Immune Responses

A number of the immune alterations induced by a stroke are also reported in severe COVID-19, including innate immune cell deficiencies, lymphopenia, and TH2-skewing. Therefore, the immunological profile of people recovering from a stroke might compound many of the deleterious immune factors elicited by COVID-19, resulting in increased disease severity and a poorer prognosis.

The Impact of COVID-19 on Stroke Patients

COVID-19 can also lead to an increased risk of stroke, and people who present to hospital with both COVID-19 and a stroke display increased mortality compared to stroke patients without COVID-19.

The immunosuppression that follows stroke may compound and exacerbate immunopathology induced by SARS-CoV-2 infection

Stroke patients are at an increased risk of developing severe COVID-19, likely due to the immunosuppression that follows a stroke. This immunosuppression may compound and exacerbate the immunopathology induced by SARS-CoV-2 infection.

Stroke-induced immunosuppression includes a reduction in the ability of monocytes and macrophages to produce pro-inflammatory cytokines and effectively present antigens. This may result in a dampened anti-viral response. Additionally, NK cells, which are critical for the anti-viral response, are reduced in the circulation of COVID-19 patients, and their functionality is impaired.

Lymphopenia is another feature of both severe COVID-19 and post-stroke immune responses. Lymphopenia is associated with an increased incidence of infection following stroke, with respiratory infection being the most common. Lymphopenia is also observed in combination with increased mobilisation of granulocytes, resulting in a high neutrophil-to-lymphocyte ratio, which has been associated with more severe COVID-19.

The cytokine response is also altered following a stroke, with a shift from a TH1 (IFNγ) to TH2 (IL-4, IL-10) phenotype. This shift is thought to foster tissue repair and protect against further brain injury, but it also contributes to infection vulnerability. A systemic bias towards TH2-associated cytokines is also associated with more severe COVID-19.

In summary, the immunosuppression that follows a stroke may compound and exacerbate the immunopathology induced by SARS-CoV-2 infection, resulting in a higher risk of severe COVID-19 in stroke patients.

The extent to which immune deficits persist after stroke is currently uncertain

The extent to which immune deficits persist after a stroke is uncertain, but several studies have been conducted to investigate this. One study found that immune alterations can be observed up to 90 days after a stroke, with systemic alterations to peripheral blood neutrophils, B and T cell signalling, and cytokine profiles. Another study found that pro-inflammatory proteins can persist for up to 7 years following a stroke.

One study found that patients with a history of stroke had a reduced ability to produce the pro-inflammatory cytokines TNF-α and IFN-γ after stimulation with the bacterial endotoxin LPS. This deficit was even more pronounced in stroke patients who developed stroke-associated infections, with further reductions in TNF-α and increased IL-10. Another study found that stroke patients had reduced ability to interact with cells of the adaptive immune system, with reduced expression of MHCII observed on splenic macrophages following experimental stroke.

In addition to the above, stroke patients also experience lymphopenia, with reduced B, T, and NK cells in the circulation. This lymphopenia was first reported in experimental animal models and subsequently detected in patients as early as 6 hours after stroke, persisting for at least 6 days. Lymphopenia is associated with an increased incidence of infection following stroke, with respiratory infection being the most common.

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