Integrative diagnostic criterion for evaluation of COVID-19 severity and the risk of post-COVID syndrome

Abstract

Pathophysiology of severe COVID-19 is characterized by changes in the number, phenotype, and function of neutrophil granulocytes (NG). Among the effector antiviral mechanisms of NG, the neutrophil extracellular traps (NETs) are among the most important features. However, their excessive formation exacerbates inflammation in acute respiratory distress syndrome and contributes to microvascular thrombosis. Their detection and counting may be important in severity grading of COVID-19, for determining correlations with clinical outcome, assessing the risk of developing post-COVID syndrome, and, possibly, for monitoring future targeted therapy. Purpose of our study was to develop a new diagnostic integrative criterion to assess the severity of COVID-19 and the risk of complications in the post-COVID period, including post-COVID signs in peripheral blood. Peripheral blood (PB) samples were studied from 31 patients with acute COVID-19 of moderate (n = 15) and severe degrees (n = 16). Moreover, we observed 52 patients discharged from the hospital after severe COVID-19, with diagnosed post-COVID syndrome (PCS) over the period of 30 to 60 days, and 100 healthy volunteers. The parameters of routine blood counts (MicroCC-20Plus) were evaluated, the leukocyte formula was calculated in PC smears, taking into account the number of formed NETs, and NGs entering pathological apoptosis. Based on the obtained results, an integral diagnostic criterion was calculated using the formula:$$ IDK = \frac{\%\ unchanged\ NG}{\%NET + \%NG\ in\ apoptosis} $$A 8.5-fold decrease in IDK index (p < 0.05) was shown in the cases of moderate-severity course of the disease, and a 30-fold drop was seen in severe cases (p < 0.05) compared with appropriate values in the group of healthy individuals. It was also found that, in 88.5% of patients with PCS after the SARS-CoV-2 infection, no morphologically altered NG were detectable in PB samples. At the same time, in 11.5% of patients with PCS, we found NETs and cells with pathological apoptosis, whereas IDC of NG-PCS was 8 times less than in the comparison group, and did not differ from the parameters of patients with moderate COVID-19 (p > 0.05) thus requiring further dispensary observation of such patients. The data obtained in this study indicate that the developed integrative diagnostic criterion allows us to assess both the severity of COVID-19 over acute period, and the risk of post-COVID syndrome. It should be emphasized that the characteristic changes in NG detected in COVID-19 may be readily identified in PB and consistently monitored by the proposed integral diagnostic criterion. A significant decrease in IDC indicates the persisting hyper-activation of NG and a need for targeted immunotherapy aimed at modulating the NG dysfunction.

Keywords

• covid-19
• post-covid syndrome
• integral diagnostic criterion
• neutrophil granulocytes
• net
• apoptosis