Biochemical and laboratory evaluations
We assessed blood group types of participants. The distribution of the ABO blood groups system in COVID-19 suspicious outpatients tested for SARS-CoV2 RT-PCR is presented in Table 1. We did not find any significant difference in terms of blood group type between negative and positive PCR groups (P =0.4).
In contrast with our results, some recent studies identified associations between ABO blood groups and COVID-19. In one previous study, 397 patients with confirmed diagnoses of COVID-19 were admitted to Imam Khomeini Hospital Complex, Tehran, Iran. Also, 500 individuals were selected to form the control group, all of whom had been disclosed to the same medical center in June 2019, before the onset of the outbreak. The results demonstrated ABO histo-blood phenotypes are correlated with patients’ susceptibility to the infection. Specifically, a higher rate of infection was observed among patients with the AB histo-blood group, while patients with the O histo-blood group had shown a lower rate of infection(18).
Also, a study on COVID-19 patients in Wuhan and Shenzhen, China, discovered associations between ABO blood types and infection. They found that the odds of having COVID-19 were higher among the A blood group and lower among the O blood group relative to the general populations of Wuhan and Shenzhen(19).
Previous work has identified similar associations between ABO blood groups and different infections or disease severity following infections, including SARS-CoV1(20), P. falciparum(21) , H. pylori(22) , Norwalk virus(23), hepatitis B virus(24), and N. gonorrhoeae(25). The difference between our observations and the results obtained in the mentioned studies may be due to differences in the population (especially in terms of race and ethnicity) or in the severity and stage of the disease.
On the other hand, there are studies whose results are in line with the results of our study. For instance, one study found insufficient evidence to conclude that the blood group distribution among all individuals tested for SARS-CoV2 is different from the general population at NYP/CUIMC (ABO: P =0.64, Rh: P =0.36)(26). Therefore, the results obtained regarding the possible relationship between blood group type and the incidence and severity of COVID-19, as well as the type of possible relationship, are still contradictory.
The results of the between-group analysis of serum levels of cortisol are shown in Table 1. Serum levels of cortisol did not show any significant differences between the two groups (P =0.4). We also categorized serum levels of cortisol as hypocortisolism (<5 μg/dL), norm cortisol (5-25 μg/dL), and hypercortisolism (˃25 μg/dL).
Cortisol serum level categories are also shown in Table 1. Our results revealed that 3.8%, 92.5%, and 3.8% of the negative PCR group presented hypo, norm, and hypercortisolism, respectively. In the positive PCR group, 7.5%, 88.7%, and 3.8% were hypo, norm, and hypercortisolism, respectively.
Immune system response plays a crucial role in controlling and resolving viral infection. Therefore, cortisol is linked to the immune system and viral infection as part of the neuroendocrine stress axis. Exogenous or endogenous glucocorticoid excess is characterized by increased susceptibility to infections due to impairments of the innate and adaptive immune systems. Thus, patients with chronic glucocorticoid excess may be at high risk of developing COVID-19 with a severe clinical course(27).
In line with our results, a descriptive and analytical cross-sectional study was conducted in a population of patients infected with 2019-nCoV in Cameroon. The researchers found no statistically significant association between serum cortisol and disease severity. Like us, they concluded that the absence of a marked rise of cortisol during COVID-19 suggests the possible involvement of the hypothalamic-pituitary-adrenal axis in this infection. However, their study did not have a non-COVID control group(28).
Another study compared baseline cortisol concentrations between COVID-19 patients and controls. Contrary to our results, they found that patients with COVID-19 presented a marked and appropriate acute cortisol stress response and that this response is significantly higher in this patient cohort than in individuals without COVID-19(29).
The observed differences, as well as individual differences in stress responses, might have arisen because COVID patients were not the same in the two studies. Specifically, they were at different stages of the disease—our study was conducted on asymptomatic/mild and moderate outpatients of COVID-19. Serum levels of aldosterone also did not show any significant differences between the two groups (P =0.2).
Table 1 shows the results of a comparison between the mean serum aldosterone levels of negative and positive PCR groups. COVID-19 and the RAAS are closely linked both in infection and in possible post-infection inflammatory cascades(7). Campana et al. reported that increased levels of aldosterone might be associated with severe forms of COVID‐19(30). This report can confirm the result obtained in our study because lower grades of the disease (mild and moderate) were evaluated in our study.
The results of a study by Henry et al., which included 30 COVID-19 patients and controls, align with our findings. They compared plasma concentrations of aldosterone between patients and controls using the Mann-Whitney U test and reported that aldosterone concentrations were comparable between patients with and without COVID-19 (8.9 (IQR:5.8-16.2) vs. 9.0 (IQR:7.4-12.2) ng/dL, P =0.865)(31).