Study identifies immune signature to predict severe COVID-19 in cardiovascular patients

By Tarun Sai LomteReviewed by Benedette Cuffari, M.Sc.May 1 2023

A recent study posted to medRxiv* preprint server assesses whether immunophenotyping in cardiovascular disease (CVD) patients could predict coronavirus disease 2019 (COVID-19) severity.

Study: Immune Signature of Patients with Cardiovascular Disease – in-Depth Immunophenotyping Predicts Increased Risk for a Severe Course of COVID-19. Image Credit: sfam_photo / Shutterstock.com

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

COVID-19 and CVD

COVID-19 severity is associated with several risk factors, including sex, age, and comorbidities that correlate with immune responses during acute infection. CVD patients are susceptible to more severe outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which can subsequently increase the risk of cardiac and pulmonary damage.

CVD patients are also at a greater risk of acute respiratory distress syndrome (ARDS), progressive respiratory failure, and pulmonary embolism due to coagulopathy associated with COVID-19. Thus, it is imperative to understand the immunologic dysfunctions underlying severe/fatal COVID-19 in this patient population to improve care and clinical outcomes.

About the study

The present study evaluated critical immune system components to predict severe COVID-19 in CVD patients.

CVD patients aged 18 or older with or without COVID-19 were eligible for inclusion. Those with viral/bacterial infections or malignancies were excluded from the study. All subjects underwent clinical/cardiac assessment within 12 hours of hospitalization.

SARS-CoV-2 infection was determined by reverse-transcription polymerase chain reaction (RT-PCR) assay. The researchers prospectively studied a cohort of 94 subjects between February and April 2020, which consisted of 37 CVD patients with COVID-19, 20 CVD patients without COVID-19, and 37 healthy donors (HDs) as controls.

Forty-five patients were males, and the participants’ median age was 58. Among CVD patients with COVID-19, 20 developed respiratory failure, while 11 required intensive care due to progressive circulatory, respiratory, or multiorgan failure. Patients with mild COVID-19 were younger than those with moderate/severe illness.

Isolated peripheral blood mononuclear cells (PBMCs) were stained with an antibody panel and measured with a flow cytometer. Unsupervised data analysis showed 40 clusters of immune cells, including B-cells, cluster of differentiation 4-positive (CD4⁺) and CD8⁺ T-cells, natural killer (NK) cells, neutrophils, basophils, innate lymphoid cells (ILCs), dendritic cell subsets, and monocytes.

Study findings

Minor differences were observed between non-infected CVD patients and HDs; however, the cell population distribution significantly differed in CVD patients with COVID-19. More specifically, infected CVD patients had more activated monocyte subsets, mature NK cells, plasmablasts, and CD4⁺ central memory T (T_cm) cells but fewer ILCs, CD8⁺ T-cell subsets, CD16⁺ monocytes, and dendritic cells as compared to non-infected CVD patients.

Pro-inflammatory cytokines such as interleukin 6 (IL-6) and IL-8 were significantly elevated in infected CVD patients relative to non-infected CVD patients. IL-6 was significantly increased in patients with severe COVID-19 as compared to those with mild COVID-19. Conversely, tumor necrosis factor (TNF), IL-33, IL-23, and IL-1b were significantly reduced in infected CVD patients, thus suggesting impaired helper T (T_h) cell differentiation.

C-C motif chemokine ligand 2 (CCL2), C-X-C chemokine ligand 9 (CXCL9), CXCL10, and CXCL11 were highly elevated during COVID-19. IL-6 and IL-8 were also significantly increased in CVD patients with severe COVID-19, whereas CCL17 was less abundant.

The team analyzed the abundance and changes in immune cell populations according to COVID-19 severity. Severe COVID-19 resulted in reduced proportions of innate immune cells. Although NK cells and CD4⁺ or CD8⁺ T-cells were higher in frequency in severe COVID-19, the expression of their functional markers was impaired, thereby suggesting an altered immune response.

The researchers also identified an immune signature characterized by a low frequency of mucosal-associated invariant T (MAIT) and intermediate effector CD8⁺ T-cells, as well as a high frequency of natural killer T (NKT) cells. This signature successfully stratified patients at high risk of severe SARS-CoV-2 infection at the time of hospital admission. Comparatively, CVD patients experiencing moderate COVID-19 only exhibited higher levels of CD8⁺ T-cells, CD8+ NKT cells, and the dendritic cell subset cDC2.

The identification of this objective immune signature could be used to differentiate between high-risk CVD who are experiencing mild or severe COVID-19. Thereafter, CVD patients suspected of having severe COVID-19 can be closely monitored and selected, if appropriate, for certain anti-inflammatory treatment strategies to ultimately prevent long-term intensive care unit (ICU) admission or death in these individuals.

Conclusions

Altered innate and adaptive immune cell frequencies were observed in CVD patients relative to HDs, which is consistent with prior studies. The chronic pro-inflammatory state associated with CVD might contribute to the observed immune signature, thus resulting in a more pronounced response to SARS-CoV-2 infection. 

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.