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

Abstract

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.

Dynamic Changes in Central and Peripheral Neuro-Injury vs. Neuroprotective Serum Markers in COVID-19 Are Modulated by Different Types of Anti-Viral Treatments but Do Not Affect the Incidence of Late and Early Strokes

“…Furthermore, ferritin is used to gauge the degree of inflammation in several inflammatory processes and COVID-19 [ 122 , 125 , 126 , 127 ]. The activation of macrophages, frequently reflected by an increase in ferritin, was suggested as one of the major drivers of COVID-19 evolution and was related to the degree of neuronal degeneration and injury in general [ 26 , 83 , 122 , 125 , 128 , 129 , 130 ]. Elevations in CCL23, a cytokine involved in the recruitment of leukocytes to nervous system compartments and linked to vascular injury-related stroke, could suggest an influx of peripheral leukocytes into the brain [ 68 , 69 , 70 ].…”

“…This conclusion supports the finding that the cerebrospinal fluid of COVID-19 patients indicates a neuronal injury but not inflammation [ 120 ]. At the same time, the activation of leukocytes persists well into COVID-19 recovery, providing a pool of inflammatory cells [ 128 ]. These activated leukocytes can be recruited into the brain via a CCL23-driven mechanism [ 67 , 69 , 120 ].…”

“…Convalescent treatment may be particularly clinically applicable as it switches off activated T cells, an important culprit in COVID-19 neuropthology [ 139 ]. Neuroprotective markers may be the non-specific effect of suppressing inflammation as the leukocytes remain activated even after treatment [ 128 , 139 ].…”

The COVID-19 "Bad Tryp" Syndrome: NAD/NADH+, Tryptophan Phenylalanine Metabolism and Thermogenesis like Hecatomb - The Hypothesis of Pathophysiology Based on a Compared COVID-19 and Yellow Fever Inflammatory Skeleton

“…5-HT2B-mediated downregulation of T cell co-stimulatory [21,[32][33][34][35][36][37][38] molecules and the simultaneous inhibition of IL-12 secretion. 5-HT2B activation results in modulation of monocyte-derived macrophage differentiation to acquire the antiinflammatory M2 phenotype and inhibition of lymphocyte proliferation, tending to imbalance to tolerance with inhibition of TH17 and stimulus to Treg [39][40][41][42].…”

“…The expression of CX3CR1 in intermediate and nonclassical monocyte subsets indicates a more phagocytic phenotype and a greater likelihood of endothelial damage. These cytokines appear to play an important role in CNS inflammation during viral encephalitis since inflammatory monocytes secrete proinflammatory cytokines such as IL-6, IL-1β and TNF-α, which have been implicated in the development of acute seizures and hippocampal damage [28,39,[54][55][56][57].…”