ELEVATED CIRCULATING MONOCYTES AND MONOCYTE ACTIVATION IN PULMONARY POSTACUTE SEQUELAE OF SARS-COV-2 INFECTION

ABSTRACT

SESSION TITLE Long COVID It Can Take Your Breath Away SESSION TYPE Original Investigations PRESENTED ON 10/16/2022 1030 am - 1130 am PURPOSE: Nearly one third of patients who recover from acute SARS-CoV2 infection will experience persistent symptoms known as Post-Acute Sequelae of SARS-CoV2 infection (PASC). Among individuals with PASC, pulmonary complications are common. Patients with severe COVID-19 have observed high systemic levels of cytokines and profound immune dysregulation. During acute SARS-CoV-2 infection, CD169, a type I interferon-inducible receptor, is overexpressed on monocytes. CD169+ macrophages are involved in hyperinflammation, viral spread, and immune regulatory function. Although monocytes/macrophage play a pivotal role in inflammation during acute SARS-CoV2 infection, less is known about how these cells contribute to lung sequelae and immunopathology in PPASC. METHODS: Cross section study conducted comparing three groups participants with PPASC with a reduced predicted diffusing capacity for carbon monoxide (DLCOc, <80%) on pulmonary function test;participants who fully recovered (RC) from SARS-CoV-2 with no residual symptoms;and healthy participants (HC) negative for SARS-CoV-2. These groups were age and gender matched from similar community settings. Among the groups, we compared the numbers of monocyte subsets (classical, intermediate and non-classical monocytes) and monocyte activation by assessing CD169 expression using flow cytometry analysis of peripheral blood mononuclear cells. RESULTS: Ten participants enrolled in each group with median age 53 years, 38.7% males. We found that PPASC and RC had higher median levels of total circulating monocytes than in HC, 59374 (IQR 43161-91523), 65661 (40049-89490) and 2689 (1378-28125), respectively (p<0.01, p<0.01). Regarding monocyte subsets based on CD14+CD16+ expression, we observed significant increase in the number of classical (CD14+CD16-), intermediate (CD14+CD16+), and non-classical (CD14-CD16+) monocytes in PPASC and RC, compared to HC (p<0.01, p=0.01, respectively). There was no difference in the number of monocytes and in the proportion of each subset between PPASC and RC. We observed increased CD169+ monocyte counts in PPASC and RC compared to HC 56.8 (23.0-92.5), 66.75 (4.3-968.7), and 2.095 (0-16.9), respectively (p<0.01, p<0.01). Furthermore, a rising trend of CD169 expression was observed in intermediate and non-classical monocytes from PPASC compared to HC. In addition, CD169+ non-classical monocytes were positively correlated with D-dimer levels in PPASC (ρ=0.72, p=0.03). CONCLUSIONS: This study present evidence that patients with COVID infection exhibit persistent alterations in monocytes even after the acute COVID infection period. Correlation of D-dimer level with CD169+ non-classical monocytes in patients with PPASC provides a further rational for determining if a specific monocyte subset contributes to the pathogenesis of PPASC. CLINICAL IMPLICATIONS Further studies are required for understanding of the development and progression of PPASC. DISCLOSURES No relevant relationships by Dominic Chow No relevant relationships by Logan Dean No relevant relationships by Gehan Devendra No relevant relationships by FRITZIE IGNO No relevant relationships by Boonyanudh Jiyarom No relevant relationships by Juwon Park No relevant relationships by Parthav Shah No relevant relationships by Cecilia Shikuma No relevant relationships by Chathura Siriwardhana