The results of the present investigation showed that the levels of D-dimer, CRP and IL-6 in patients with COVID-19 were significantly increased compared to those in normal subjects, while the level of HIF-1α was significantly decreased in patents with COVID-19 compared to that in normal individuals. Furthermore, the findings indicated that there is a significant and direct correlation between IL-6 and CRP and D-dimer, although a negative and significant correlation was observed between HIF-1α and D-dimer, IL-6 and CRP. It has been shown that coagulation disorders are present in patients with COVID-19 (10); under these conditions, the activity of the fibrinolytic system is increased, and D-dimer is formed from fibrin (11). Thus, increasing the level of D-dimer is an indicator for coagulation disorders associated with COVID-19 infection (11, 12), and it has been shown that the level of D-dimer is significantly elevated during COVID-19 (13). Our observation indicated that the level of D-dimer was significantly elevated in COVID-19 patients, and our finding was parallel with the results of previous studies, which had similar observations (14–16).
Inflammation has a crucial function in COVID-19 disease pathogenesis, and one of the most important indicators during inflammatory conditions is CRP. CRP is mainly secreted by hepatocytes, and as one of the acute phase proteins, its level increases during inflammation and infectious diseases (17). There is evidence that indicates that the CRP level significantly increases during SARS-CoV-2 infection. On the other hand, it has been shown that CRP is associated with the severity of COVID-19 and acts as a prognostic factor during SARS-CoV-2 infection (18, 19). We observed a significant increase in CRP levels in COVID-19 patients compared to those in the control group (normal subjects). Our data were parallel with the results of Liu et al., who observed a significant elevation in CRP levels in COVID-19 patients (20). Additionally, several studies have indicated that patients with COVID-19 have high levels of CRP, and our findings were consistent with these findings (18, 21, 22). On the other hand, it has been shown that CRP levels increase in response to IL-6 during inflammation (23); thus, in the next step, we assessed the level of IL-6 in the studied groups and found that IL-6 levels in patients were significantly increased compared to those in subjects. IL-6 is considered a pleotropic cytokine that participates in the inflammatory response, and it has been shown that this cytokine has a crucial function in tissue injury during SARS-CoV-2 infection (24, 25). The cause of increasing the level of IL-6 during SARS-CoV-2 infection might be associated with the increased secretion of this cytokine by monocytes and macrophages, which is induced by the virus. Our assessment showed that the case group (patients with COVID-19) had higher levels of IL-6. Interestingly, we observed that the level of IL-6 in patients hospitalized in the ICU was higher than that in the outpatient group, and these findings proposed that IL-6 could be associated with the severity of COVID-19. Furthermore, we observed a significant correlation between IL-6 and D-dimer, indicating that IL-6 might be associated with coagulation disorders in SARS-CoV-2 infection.
One of the most important hypotheses of the present study was the investigation of HIF-1α in the studied groups and its correlation with inflammatory parameters. Several studies have proposed that HIF-1α, by initiating cytokine storms during COVID-19, might be associated with disease severity (8, 26, 27). In contrast, there is evidence suggesting that HIF-1α might have a protective role during COVID-19 by decreasing the level of ferritin and downregulating ACE-2, which acts as a SARS-CoV-2 virus receptor (28–30). Our observations showed that the level of HIF-1α was significantly decreased in the case group compared to the normal subject group. Additionally, we showed a significant and negative correlation between HIF-1α and inflammatory parameters and D-dimer, and our findings suggested that HIF-1α might have a protective role in SARS-CoV-2 infection and COVID-19.