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

Intense monocyte activation and infiltration into the target tissues is the main mechanism of lung injury in SARS CoV2 infection. A reduction in the degree and nature of such cellular responses is expected following recovery. We aimed to investigate the immune responses in severe Covid-19 patients and recovered patients. Methods Severe COVID-19 patients (n=34) at Lok Nayak Hospital, New Delhi and COVID-19 recovered patients (n=15) from mild disease and considered for convalescent plasma (COPLA) donation at Institute of Liver and Biliary Sciences (ILBS), New Delhi were recruited. We performed a multiplex cytokine bead assay in plasma and detailed multicolour flow cytometric analysis in peripheral blood of both groups and outcomes were compared in both groups and with healthy controls (n=10). Results A significant increase in inflammatory markers [MIP1-a, MIP3a, MCP1, MIF, MMP12, ITAC, VEGF-A, and leptin] was observed in severe patients. Non-survivors additionally showed increased IL-6 levels. Despite the sustained expression of MIPs, the recovered patients showed a surge in MCSF and IL-18 levels. Both the groups had increased CCR2, CX3CR1 positive monocytes, low CD8 T cells, APRIL and BAFFR+ve B cells compared with healthy subjects. In conclusion, patients who have recovered and considered for COPLA donations still have compromised immunity with sustained expression of inflammatory monocytes and activated T cells. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The study was supported by intramural funding of the corresponding author. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was performed in accordance with Institutional Ethical Committee approval (No.F.37/(1)/9/ILBS/DOA/2020/20217/260). All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Yes, I agree * COPLA donors : (Convalescent Plasma donors) HC : (Healthy Controls) APRIL : (A proliferation-inducing ligand) BAFFR : (B-cell activating factor receptor) (DCs) : Dendritic cells PCR : (Polymerase Chain Reaction) IL : (Interleukins) IFN : (Interferon) TGF-b : (Transforming growth factor b) MIP : (macrophage inflammatory protein MCP : (Monocyte chemoattractant protein ITAC : (interferon-inducible T-cell α chemoattractant) ENA78 : (neutrophil-activating peptide) VEGF : (vascular endothelial growth factor) IP-10 : (IFN-γ inducible protein 10) MMP : (Matrix metalloproteinase) RR : (respiratory rate) PaO2 : (Partial pressure of oxygen) FiO2 : (fraction of inspired oxygen) COPD : (Chronic obstructive pulmonary disease) BMI : (Body Mass Index) CBC : (Complete blood count) HIV : (Human Immunodeficiency virus) PBMC : (peripheral blood mononuclear cells) (WB) : Whole blood (SD) : Standard deviation SOFA score : (Sequential Organ Failure assessment score)