■内质网(ER)是蛋白质合成的位点,它的折叠和分泌。一套复杂的信号通路,所谓的UPR途径,是由哺乳动物细胞中的ER进化而来的,允许细胞响应内质网内错误折叠蛋白的存在。通过针对疾病的未折叠蛋白质的积累破坏这些信号传导系统可能导致细胞应激。这项研究的目的是探讨COVID-19感染是否导致这种内质网相关应激(ER-stress)。通过检查ER应激标志物例如PERK(适应)和TRAF2(警报)的表达来评估ER应激。ER应激与几种血液参数相关。IgG,促炎和抗炎细胞因子,白细胞,淋巴细胞,红细胞,COVID-19受影响受试者的血红蛋白和PaO2/FiO2比值(动脉氧分压与吸入氧气分数之比)。发现COVID-19感染是一种蛋白质稳态(蛋白质稳态)崩溃状态。IgG水平的变化显示受感染受试者的免疫应答非常差。在疾病的初始阶段,促炎细胞因子水平较高,抗炎细胞因子水平较低;尽管它们在疾病后期部分受损.随着时间的推移,总白细胞浓度增加;而淋巴细胞的百分比下降。在RBC计数和血红蛋白(Hb)水平的情况下未观察到显着变化。RBC和Hb均维持在其正常范围内。在轻度压力组,PaO2/FiO2比率(氧合状态)处于正常范围的较高侧;而在其他两组中,该比率处于呼吸窘迫综合征模式。病毒可以诱发轻度到重度的内质网应激,这可能是细胞死亡和全身功能障碍的原因,导致致命的后果。
■SARS-CoV-2感染和相关后果的示意图。
UNASSIGNED: The endoplasmic reticulum (ER) is the site for protein synthesis, its folding and secretion. An intricate set of signalling pathways, called UPR pathways, have been evolved by ER in mammalian cells, to allow the cell to respond the presence of misfolded proteins within the ER. Breaching of these signalling systems by disease oriented accumulation of unfolded proteins may develop cellular stress. The aim of this
study is to explore whether COVID-19 infection is responsible for developing this kind of endoplasmic reticulum related stress (ER-stress). ER-stress was evaluated by checking the expression of ER-stress markers e.g. PERK (adapting) and TRAF2 (alarming). ER-stress was correlated to several blood parameters viz. IgG, pro- and anti-inflammatory cytokines, leukocytes, lymphocytes, RBC, haemoglobin and PaO2/FiO2 ratio (ratio of arterial oxygen partial pressure to fractional inspired oxygen) in COVID-19 affected subjects. COVID-19 infection was found to be a state of protein homeostasis (proteostasis) collapse. Changes in IgG levels showed very poor immune response by the infected subjects. At the initial phase of the disease, pro-inflammatory cytokine levels were high and anti-inflammatory cytokines levels were low; though they were partly compromised at later phase of the disease. Total leukocyte concentration increased over the period of time; while percentage of lymphocytes were dropped. No significant changes were observed in cases of RBC counts and haemoglobin (Hb) levels. Both RBC and Hb were maintained at their normal range. In mildly stressed group, PaO2/FiO2 ratio (oxygenation status) was in the higher side of normal range; whereas in other two groups the ratio was in respiratory distress syndrome mode. Virus could induce mild to severe ER-stress, which could be the cause of cellular death and systemic dysfunction introducing fatal consequences.
UNASSIGNED: Schematic representation of SARS-CoV-2 infection and related consequences.