Sustained expression of inflammatory monocytes and activated T cells in COVID-19 patients and recovered convalescent plasma donors

Introduction: Intense monocyte activation and infiltration into the target tissues are the main mechanisms of lung injury in severe acute respiratory syndrome coronavirus 2 infection. A reduction in the degree and nature of such cellular responses is expected following recovery. We aimed to investigate the immune responses in moderate coronavirus disease 2019 (COVID-19) patients and recovered patients.

Methods: Moderate COVID-19 patients (n = 34) at Lok Nayak Hospital, New Delhi, and COVID-19 recovered patients (n = 15) from the mild disease who were considered for convalescent plasma (COPLA) donation at the Institute of Liver and Biliary Sciences, New Delhi and healthy individuals (n = 10), were recruited. We have assessed 21 plasma cytokines using cytokine bead array, performed proteomics on serum proteins, and analyzed immune cells using a detailed multicolor flow cytometry.

Results: A significant increase in inflammatory markers such as macrophage inflammatory protein (MIP)1-α, monocyte chemotactic protein-1, macrophage migration inhibitory factor, vascular endothelial growth factor-A, and Leptin was observed in the moderate patients. Nonsurvivors additionally showed increased interleukin (IL)-6 levels. Consistently, the proteomics analysis showed the signatures of cytokine production and interferon-γ response, and increased level of acute-phase protein SAA1 in the serum of COVID-19 patients. Despite the sustained expression of MIPs, the recovered COPLA donors showed a surge in MCSF and IL-18 levels. Both the groups had increased CCR2, CX3CR1 positive monocytes, low CD8⁺ T cells, A proliferation-inducing ligand, and B-cell activating factor receptor⁺ B cells compared with healthy subjects.

Conclusions: Patients who have recovered and considered for COPLA donations still have compromised immunity with sustained expression of inflammatory monocytes and activated T cells.