Dysregulated monocyte compartment in PACS patients

Abstract

Introduction: 1-5% of all patients with COVID-19, a disease caused by infection with Severe Acute Respiratory Syndrome Virus 2 (SARS-Cov-2), even those with mild COVID-19 symptoms, continue to have symptoms after initial recovery. Symptoms associated with the post-acute sequelae of COVID-19 (PACS) include, among others, fatigue, shortness of breath, cough, and cognitive dysfunction. Since the dysregulated immune response appears to be caused by the sustained activation of certain immune cells, including monocytes, and the release of specific cytokines, the aim of our study was to investigate the effect of PACS disease on monocyte subpopulations.

Methods: Twenty-two healthy and thirty-two patients with PACS were included into this study. We performed blood gas analysis and measured hematological parameters from peripheral blood of PACS patients and compared them with healthy donors. Surface markers to identify monocyte subpopulations were analyzed by flow cytometry.

Results: PACS patients had higher numbers of intermediate and CD56+ monocytes, whereas the numbers of total monocytes, classical and non-classical monocytes were normal compared to healthy donors. Comparison of patients with and without fatigue, cough, and dyspnea showed no difference in monocyte subset frequencies. However, patients with cognitive dysfunction had increased numbers of non-classical monocytes compared to patients without this symptom.

Discussion: This suggests a disturbed homeostasis of the monocyte subsets in the peripheral blood of patients with PACS.

Keywords: CD56+ monocytes; COVID-19; PACS; SARS-CoV-2; intermediate monocytes; monocytes.

Figure 1

Comparison of total monocyte numbers of healthy controls and PACS patients. (a) Absolute numbers of total monocytes of healthy controls (HC, n = 22) and PACS patients (PACS, n = 32). Scatter plots show mean ± SEM. (b) Absolute numbers of total monocytes of healthy controls (HC, n = 22) and PACS patients without fatigue (n = 6) and with fatigue (n = 26). (c) Absolute numbers of total monocytes of healthy controls (HC, n = 22) and PACS patients without cough (n = 8) and with cough (n = 24). (d) Absolute numbers of total monocytes of healthy controls (HC, n = 22) and PACS patients without dyspnea (n = 3) and with dyspnea (n = 29). (e) Absolute numbers of total monocytes of healthy controls (HC, n = 22) and PACS patients without cognitive dysfunction (n = 23) and with cognitive dysfunction (n = 9). Scatter plots show mean ± SEM. Statistical analysis was performed using two-tailed Mann–Whitney U test (a) or Kruskall-Wallis test with Dunn’s test (b-e). ns, not significant.

Figure 2

Comparison of classical monocyte numbers of healthy controls and PACS patients. (a) Absolute numbers of classical monocytes of healthy controls (HC, n = 22) and PACS patients (PACS, n = 32). Scatter plots show mean ± SEM. (b) Absolute numbers of classical monocytes of healthy controls (HC, n = 22) and PACS patients without fatigue (n = 6) and with fatigue (n = 26). (c) Absolute numbers of classical monocytes of healthy controls (HC, n = 22) and PACS patients without cough (n = 8) and with cough (n = 24). (d) Absolute numbers of classical monocytes of healthy controls (HC, n = 22) and PACS patients without dyspnea (n = 3) and with dyspnea (n = 29). (e) Absolute numbers of classical monocytes of healthy controls (HC, n = 22) and PACS patients without cognitive dysfunction (n = 23) and with cognitive dysfunction (n = 9). Scatter plots show mean ± SEM. Statistical analysis was performed using two-tailed Mann–Whitney U test (a) or Kruskall-Wallis test with Dunn’s test (b-e). ns, not significant.

Figure 3

Comparison of intermediate monocyte numbers of healthy controls and PACS patients. (a) Absolute numbers of intermediate monocytes of healthy controls (HC, n = 22) and PACS patients (PACS, n = 32). Scatter plots show mean ± SEM. (b) Absolute numbers of intermediate monocytes of healthy controls (HC, n = 22) and PACS patients without fatigue (n = 6) and with fatigue (n = 26). (c) Absolute numbers of intermediate monocytes of healthy controls (HC, n = 22) and PACS patients without cough (n = 8) and with cough (n = 24). (d) Absolute numbers of intermediate monocytes of healthy controls (HC, n = 22) and PACS patients without dyspnea (n = 3) and with dyspnea (n = 29). (e) Absolute numbers of intermediate monocytes of healthy controls (HC, n = 22) and PACS patients without cognitive dysfunction (n = 23) and with cognitive dysfunction (n = 9). Scatter plots show mean ± SEM. Statistical analysis was performed using two-tailed Mann–Whitney U test (a) or Kruskall-Wallis test with Dunn’s test (b-e). ns, not significant.

Figure 4

Comparison of non-classical monocyte numbers of healthy controls and PACS patients. (a) Absolute numbers of non-classical monocytes (NCM) of healthy controls (HC, n = 22) and PACS patients (PACS, n = 32). Scatter plots show mean ± SEM. (b) Absolute numbers of non-classical monocytes of healthy controls (HC, n = 22) and PACS patients without fatigue (n = 6) and with fatigue (n = 26). (c) Absolute numbers of non-classical monocytes of healthy controls (HC, n = 22) and PACS patients without cough (n = 8) and with cough (n = 24). (d) Absolute numbers of non-classical monocytes of healthy controls (HC, n = 22) and PACS patients without dyspnea (n = 3) and with dyspnea (n = 29). (e) Absolute numbers of non-classical monocytes of healthy controls (HC, n = 22) and PACS patients without cognitive dysfunction (n = 23) and with cognitive dysfunction (n = 9). (f) D-dimer concentration in the serum of PACS patients without cognitive dysfunction (n = 23) and with cognitive dysfunction (n = 9). (a-f) Scatter plots show mean ± SEM. Statistical analysis was performed using two-tailed Mann–Whitney U test (a, f) or Kruskall-Wallis test with Dunn’s test (b-e). (g) Correlation of absolute numbers of non-classical monocytes of PACS patients without cognitive dysfunction with carboxylated hemoglobin (COHb) (n = 23). Spearman correlation coefficient and level of significance as indicated. ns, not significant.

Figure 5

Comparison of CD56+ monocyte numbers of healthy controls and PACS patients. (a) Absolute numbers of CD56+ monocytes of healthy controls (HC, n = 22) and PACS patients (PACS, n = 32). Scatter plots show mean ± SEM. (b) Absolute numbers of CD56+ monocytes of healthy controls (HC, n = 22) and PACS patients without fatigue (n = 6) and with fatigue (n = 26). (c) Absolute numbers of CD56+ monocytes of healthy controls (HC, n = 22) and PACS patients without cough (n = 8) and with cough (n = 24). (d) Absolute numbers of CD56+ monocytes of healthy controls (HC, n = 22) and PACS patients without dyspnea (n = 3) and with dyspnea (n = 29). (e) Absolute numbers of CD56+ monocytes of healthy controls (HC, n = 22) and PACS patients without cognitive dysfunction (n = 23) and with cognitive dysfunction (n = 9). Scatter plots show mean ± SEM. Statistical analysis was performed using two-tailed Mann–Whitney U test (a) or Kruskall-Wallis test with Dunn’s test (b-e). ns, not significant.