ABSTRACT
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. MethodsSevere 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). ResultsA 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.
ABSTRACT
BackgroundThe role of convalescent plasma (COPLA) for the treatment of severely ill Corona Virus Disease-2019 is under investigation. We compared the efficacy and safety of convalescent plasma with fresh frozen plasma (FFP) in severe COVID-19 patients. Methods and findingsThis was an open-label, single-centre phase II RCT on 29 patients with severe COVID-19 from India. One group received COPLA with standard medical care (SMC) (n=14), and another group received FFP with SMC (n=15). A total of 29 patients were randomized in the two treatment groups. Eleven out of 14 (78.5%) patients remained free of ventilation at day seven in the intervention arm while the proportion was 14 out of 15 (93.3 %) in the control arm (p= 0.258). The median reductions in RR per min at 48-hours in COPLA-group and FFP group were -6.5 and -3 respectively [p=0.004] and at day seven were -14.5 and -10 respectively (p=0.008). The median improvements in percentage O2 saturation at 48-hours were 6.5 and 2 respectively [p=0.001] and at day seven were 10 and 7.5 respectively (p=0.026). In the COPLA-group, the median improvement in PaO2/FiO2 was significantly superior to FFP at 48-hours [41.94 and 231.15, p=0.009], and also at day-7 [5.55 and 77.01 p<0.001]. We did not find significant differences in hospitalization duration between the groups (0.08). ConclusionCOPLA therapy resulted in rapid improvement in respiratory parameters and shortened time to clinical recovery, although no significant reduction in mortality was observed in this pilot trial. We need larger trials to draw conclusive evidence on the use of Convalescent plasma in COVID-19. This trial is registered with ClinicalTrial.gov (identifier: NCT04346446).
