In this retrospective cohort study, racial/ethnic differences were compared in the likelihood of COVID-19 positive, signs and symptoms, and clinical outcome (Table 6). We also investigated whether any differences in outcomes were associated with age, sex, and comorbidities. All assessments were performed in all hospitalized (suspected/confirmed COVID-19) and confirmed COVID-19 patients. First, we explain the racial differences in disease severity among all hospitalized patients, then among confirmed patients. In the following, we will describe the difference in the mortality rate among all hospitalized patients as well as confirmed patients.
Table 6
Odds Ratios of death by Race/Ethnicity
| Base Model (Unadjusted) | Model 1 | Model 2 |
Population | Race/ethnicity | OR (95% CI) | P value | OR (95% CI) | P value | OR (95% CI) | P value |
All Hospitalized Patients | Iranian | 1 [Reference] | > .99 | 1 [Reference] | > .99 | 1 [Reference] | > .99 |
Afghan | 1.037 (0.70–1.5) | 0.855 | 1.57 (1.03–2.4) | 0.036 | 1.66 (1.08–2.55) | 0.020 |
COVID-19 Positive Patients | Iranian | 1 [Reference] | > .99 | 1 [Reference] | > .99 | 1 [Reference] | > .99 |
Afghan | 1.46 (0.95–2.2) | 0.078 | 2.27 (1.43–3.6) | 0.000 | 2.34 (1.47–3.72) | 0.000 |
Table 6
The results showed the highest incidence of COVID-19 in Afghan patients at a younger age than Iranians. The findings were similar to other studies, which reported COVID-19 incidence to be highest among 20–40 years old Afghan patients (17, 18). This may be since over half of the Afghan population is under the age of 20 (17). Based on PCR test and CT scan results, the prevalence of confirmed COVID-19 positive was significantly higher in Iranians than Afghans (P < 0.001).
According to the present study, among all hospitalized (suspected/confirmed COVID-19) patients, signs and symptoms, respiratory distress, muscular pain, anorexia, headache, convulsions, smell loss, chest pain, taste loss, and vertigo were significantly more represented in Iranians than Afghans. Furthermore, the severe disease was more common in Iranians than Afghans (P < 0.001). Although several studies have reported that individuals with older age and comorbidities are facing a higher risk of COVID-19 susceptibility and severity, but in our study this difference could not be explained only by the higher mean age of Iranians or the underlying diseases; Because the risk of severity remains still high in Iranian patients after adjusting for age, sex, and comorbidities, (OR, 0.69; 95%CI, 0.56–0.88; P < 0.003) (19–21). This racial difference in disease severity may be related to the immune response to infection. This is well known that genetic differences contribute to individual variations in the immune response to pathogens (22). Recently, Upadhyai et al. have reported a significant variation in genetic variants involved in host immune-related pathways, such as innate and adaptive immune system, interleukin (IL) signaling, interferon (IFN) signaling, cytokine signaling, as well as antigen processing by major histocompatibility complex (MHC) between asymptomatic and severe COVID-19 patients (23). Cellular ACE2 expression varies among individuals and ethnicities. Differences in ACE2 expression and variants might influence susceptibility to SARS-CoV-2 infection and disease severity (24, 25). Furthermore, the frequency of the ACE1 II genotype is inversely related to susceptibility to COVID-19. This genotype was less frequent among the Iranian population (26, 27). Also, the TMPRSS2 gene serves as an activator of SARS-CoV entry into the host cells. Iranians showed more expression of TMPRSS2. These may be related to increased COVID-19 susceptibility and severity among them (28, 29). In addition to genetic factors, some epigenetic factors, such as histone modification (H3K4me1, H3K4me3, H3K27Ac) in the ACE2 gene and decreased DNA methylation of the ACE2 promoter increase the expression of ACE2, affecting, in turn, the risk and severity of COVID disease (30, 31).
Among confirmed patients, respiratory distress and anorexia were more common in Iranians than Afghans. Although the rate of comorbidities was higher in Iranians, no significant race/ethnicity difference was observed in the severity of the disease among confirmed patients even after adjusting for age, sex, and comorbidities.
No significant race/ethnicity disparity was observed concerning the mortality rate. However, by adjusting for age, sex, and comorbidity, a significant difference was observed in all hospitalized patients (OR, 1.66; 95%CI, 1.08–2.55; P = 0.020), with being more significant among confirmed COVID-19 patients (OR, 2.34; 95%CI, 1.47–3.72; P = 0.000). Indeed, Afghans suffered almost twice as many deaths as Iranians. Although some studies have linked differences in mortality to variations in treatment protocols in different health care centers, this is not the case with the present study; this is since this study was performed in a single hospital with a distinct treatment protocol for all patients (32–34). Therefore, other factors are involved in this difference. Researches shows that some medications taken by patients improved the survival rate of COVID-19 cases. Cardiovascular drugs (e.g., ACE inhibitors), statin and anticoagulant drugs, anti-diabetic drugs (e.g., Metformin and dipeptidyl peptidase 4 inhibitors mentioned (DPP4-I)) are among these medications (35–40). Since Iranian patients had more comorbidity than Afghans, consumption of cardiovascular, antihypertensive, and anti-diabetic drugs might have a protective effect against COVID-19 and improve survival. Some studies demonstrated that ARDS outcomes also differ in various ethnicities, even after adjusting for age, sex, disease severity, type of hospital and median household income (41, 42). Candidate genes associated with ARDS have been identified to be including reactive oxygen species, innate immunity-related inflammation and endothelial vascular signaling pathways. Ethnicity might affect cytokine gene polymorphisms and inflammatory profiles in specific conditions, In a way some ethnic groups more disposed to a heightened inflammatory response (43, 44). In addition, it should be noted that social and economic factors may also affect inflammatory pathways and gene expression that poorly understood and should be further considered in future studies (45).
In addition to the above, another factor affecting the mortality rate due to covid-19 is the delay in diagnosis. Studies show that people who are diagnosed longer after the onset of symptoms face higher mortality. Some reasons for delayed care-seeking behavior could be prohibitory costs, lack of access to health care services and stigmatization (46). Social stigma can disrupt the process of diagnosis and treatment by negatively affecting social communication. People who feel stigmatized may avoid behaviors that increase stigma, including following health protocols and wearing masks to prevent covid-19. There has been a report of suspected covid-19 patients escaping from a hospital in Afghanistan (47). The people of Afghanistan considered the hospital environment to be more caring than therapeutic. Furthermore, the fear of social stigma prevented them from going to the hospital. Therefore, they prefer home care to visiting the hospital (48). On the other hand, Afghan immigrants have fragile economic conditions due to their daily work; also not having insurance, they incur high medical expenses. Therefore, delaying medical care due to social stigma and economic situation may explained more intubation and the increased median duration of hospital stay that lead to more mortality rate in afghans (49–51).