Similar Clinical Course and Significance of Circulating Innate and Adaptive Immune Cell Counts in STEMI and COVID-19

Abstract

This study aimed to assess the time course of circulating neutrophil and lymphocyte counts and their ratio (NLR) in ST-segment elevation myocardial infarction (STEMI) and coronavirus disease (COVID)-19 and explore their associations with clinical events and structural damage. Circulating neutrophil, lymphocyte and NLR were sequentially measured in 659 patients admitted for STEMI and in 103 COVID-19 patients. The dynamics detected in STEMI (within a few hours) were replicated in COVID-19 (within a few days). In both entities patients with events and with severe structural damage displayed higher neutrophil and lower lymphocyte counts. In both scenarios, higher maximum neutrophil and lower minimum lymphocyte counts were associated with more events and more severe organ damage. NLR was higher in STEMI and COVID-19 patients with the worst clinical and structural outcomes. A canonical deregulation of the immune response occurs in STEMI and COVID-19 patients. Boosted circulating innate (neutrophilia) and depressed circulating adaptive immunity (lymphopenia) is associated with more events and severe organ damage. A greater understanding of these critical illnesses is pivotal to explore novel alternative therapies.

Keywords: COVID-19; lymphocyte; myocardial infarction; neutrophils; prognosis; severity.

Figure 1

Flowchart of the STEMI study group, showing STEMI patient recruitment (A) and blood sampling (B). MR: magnetic resonance; PCI: primary coronary intervention; STEMI: ST-segment elevation myocardial infarction.

Figure 2

Extension of structural damage. In STEMI patients (upper panel), CMR images of extensive (left) and non-extensive (right) infarct size. In COVID-19 patients (lower panel), CT studies of bilateral (left) and unilateral (right) pneumonia. CMR: cardiac magnetic resonance. COVID-19: coronavirus disease 2019. CT: computed tomography. STEMI: ST-segment elevation myocardial infarction.

Figure 3

Flowchart of the COVID-19 study group, showing COVID-19 patient recruitment (A) and blood sampling (B). COVID-19: coronavirus disease 2019; CT: computed tomography.

Figure 4

Evolution of neutrophil and lymphocyte counts and NLR after reperfused STEMI and COVID-19. Time course of median neutrophil and lymphocyte (×1000 cells/mL) counts and NLR in the entire cohort of STEMI patients (A,C,E, respectively) and COVID-19 (B,D,F, respectively). Data were expressed as median [quartile 25-quartile 75]. Dotted lines represent the upper and lower ranges of normality. COVID-19: coronavirus disease 2019; NLR: neutrophil-to-lymphocyte ratio; STEMI: ST-segment elevation myocardial infarction.

Figure 5

Time course of neutrophil and lymphocyte counts and NLR according to occurrence of adverse events. In STEMI (n = 659), MACE included death, and readmission for heart failure. Evolution of median neutrophil (A) and lymphocyte (C) (×1000 cells/mL) counts as well as NLR (E) according to MACE. In COVID-19 patients (n = 103), adverse events were defined as death and/or admission in ICU. Dynamics of median neutrophil (B) and lymphocyte (D) (×1000 cells/mL) counts as well as NLR (F) according to adverse events. Data were expressed as median [quartile 25-quartile 75]. Dotted lines represent the upper and lower ranges of normality. * p < 0.05, ** p < 0.01, *** p < 0.001. COVID-19: coronavirus disease 2019; ICU: intensive care unit; MACE: major adverse cardiac events; NLR: neutrophil-to-lymphocyte ratio; STEMI: ST-segment elevation myocardial infarction.

Figure 6

Dynamics of circulating neutrophil and lymphocyte counts and NLR according to structural damage after reperfused STEMI and COVID-19. In STEMI, patients were dichotomized according to the extension of CMR-derived infarct size (extensive: >30% of LV mass and non-extensive: <30% of LV mass). Time course of median neutrophil (A) and lymphocyte (C) (×1000 cells/mL) counts as well as NLR (E) depending on infarct size. In COVID-19, patients were dichotomized according to the extension of CT-derived bilateral pneumonia. Time course of median neutrophil (B) and lymphocyte (D) (×1000 cells/mL) counts as well as NLR (F) depending on the presence of bilateral pneumonia. Data were expressed as median [quartile 25-quartile 75]. Dotted lines represent the upper and lower ranges of normality. * p < 0.05, ** p < 0.01, *** p < 0.001. CMR: cardiac magnetic resonance; COVID-19: coronavirus disease 2019; CT: computed tomography; LV: left ventricular; NLR: neutrophil-to-lymphocyte ratio; STEMI: ST-segment elevation myocardial infarction.

Figure 7

Association of maximum neutrophil and minimum lymphocyte count as well as maximum NLR with occurrence of adverse events and severe structural damage. Maximum neutrophil count (A,B), minimum lymphocyte count (C,D), and maximum NLR (E,F) as related to presence of adverse events (left panel) or severe structural damage (right panel). In STEMI patients, MACE included death and/or readmission for heart failure, whereas in the COVID-19 cohort, death and/or admission in ICU were regarded as adverse events. With respect to structural damage, STEMI patients were dichotomized according to CMR-derived infarct size and COVID-19 depending on the presence of bilateral pneumonia in either chest X-ray or CT images. Data were expressed as median [quartile 25-quartile 75]. Dotted lines represent the upper and lower ranges of normality. CMR: cardiac magnetic resonance; COVID-19: coronavirus disease 2019; CT: computed tomography; ICU: intensive care unit; MACE: major adverse cardiac events; NLR: neutrophil-to-lymphocyte ratio; STEMI: ST-segment elevation myocardial infarction.

Figure 8

Percentage of patients experiencing adverse events or severe structural damage according to maximum NLR in STEMI and COVID-19 cohorts. Both populations were dichotomized according to the median value of maximum NLR (STEMI: 7 and COVID-19: 8). Percentage of patients showing adverse events: (A) STEMI: death and/or heart failure; (B) COVID-19: death and/or admission into ICU) or severe structural damage; (C) STEMI: CMR-derived infarct size >30% of left ventricular mass; (D) COVID-19: CT-derived bilateral pneumonia) according to maximum NLR. CMR: cardiac magnetic resonance; COVID-19: coronavirus disease 2019; CT: computed tomography; ICU: intensive care unit; NLR: neutrophil-to-lymphocyte ratio; STEMI: ST-segment elevation myocardial infarction.