This research is a multicentre descriptive study on the socio-demographic determinants and clinical characteristics of a large group of 205,654 patients with COVID-19. The main findings showed that older age (60 and older), male sex, residing in the north and east region of the province, having a positive history for opioids dependency, and having COVID-19 exposure history were associated with low levels of blood oxygen saturation in patients infected with SARS-CoV-2. Patients suffering from comorbidities including diabetes, hypertension, cardiovascular diseases, chronic respiratory, and chronic kidney diseases were more likely to develop low SpO2 levels. Clinical manifestations correlated with the COVID-19 related hypoxia were fever, muscle ache, difficulty breathing, diarrhea, headache, impaired consciousness, and skin lesions. The positive predictors of mortality due to COVID-19 were older age (60 and older), male sex, residing in the public health region of central and south, and having COVID-19 exposure history. Comorbidities containing cancer, asthma, chronic respiratory diseases, chronic liver and chronic kidney diseases, chronic neurological disorders, and HIV/AIDS infection were associated with higher risk of death in patients infected with SARS-CoV-2. Fever, cough, muscle ache, difficulty breathing, SpO2 ≤ 93, nausea, headache, and impaired consciousness were clinical presentations with increased odds of COVID-19 mortality. Smoking revealed a protective effect against both the low blood oxygen saturation levels and death in patients with SARS-CoV-2 infection.
The mean age of patients in our study was 53 years old, which was in line with the estimated mean age of COVID-19 patients for outside China (52.5 years old) stated in a systematic review of 10 regions from around the globe. However, it was higher than the findings in China, where the mean age of patients was reported as 46 years old [15]. Compared to a study conducted in Iran early in the epidemic (57.3 years), a slight decrease was noticeable in the mean age of patients with SARS-CoV-2 infection [10]. This age shift could be related partly to the increased number of younger adults returning to workplaces and universities in the past few months. In this study, a greater number of men were infected with SARS-CoV-2 than women (male to female ratio of 1.2). This pattern was observed in most countries and might be attributed to the biological factors which make men generally more susceptible to viral infections [16, 17]. Counts were highest in the public health region of North and East. However, since this public health unit covers a greater proportion of people in the province compared to the other two public health units, this finding was consistent with the expectations. The most common comorbidity reported in COVID-19 patients was hypertension, followed by diabetes, and cardiovascular diseases. The results were aligned with findings from a systematic review of 9249 patients with SARS-CoV-2 infection [18]. The possible explanation for high rates of the abovementioned underlying diseases in patients with COVID-19, is the increased expression of angiotensin-converting enzyme 2 (ACE2) receptors in patients with diabetes and in hypertensive patients treated with ACE2 stimulating medications. ACE2 is believed to have an important role in the SARS-CoV-2 entry into human cells [19]. In accordance with previous studies, the top three common symptoms on admission included cough, difficulty breathing, and fever. Yet considering gastrointestinal presentations, the most common symptoms in this study were nausea and loss of appetite, while diarrhea was the major gastrointestinal complaint reported in literature from outside Iran [9, 15, 20].
Our study revealed that about half of the patients with COVID-19 infection, were suffering from hypoxia at the time of admission, which was higher than the rate reported from China 36%, but lower than the rate in the United States (65%) [21, 22]. However, results must be interpreted with caution given the differences in the age structure and disease severity between the study populations. The ICU admission rate in this study (17.8% of admitted patients) was low in comparison with China (23%), and Italy (21%) [20, 23]. These differences can be justified with the presence of a large proportion of young adults in patients who have been diagnosed with the disease during the epidemic in Tehran. At data cut-off for this study, the overall death rate was 10%, but additional mortalities may happen in those still hospitalised. The overall mortality rate was higher than estimates from Italy (5.6%) or New Zealand (1.5%), but consistent with the estimated death rate in China (11%). The higher death rate obtained in our analysis, could be related to the three consecutive surges of COVID-19 cases during the epidemic. However, it is worth mentioning that the estimated death rates are affected by the number of the tests performed. Higher mortality rates could result when the denominator, the number of the infected individuals, are smaller due to lower testing [24]. Therefore, generalization of the observed mortality rate to the whole population is not recommended.
In the multivariate analysis, patients with the age of 60 and older and male sex were more likely to present with low SpO2 levels on admission, and ultimately die as the result of the disease, which confirms previous findings [6, 11, 20]. Residing in the public health region of North and East was associated with higher risk of low blood oxygen saturation levels in infected patients, whereas, the probability of death was higher for residents of the public health unit of Central and South. Generally north and east areas have higher altitude compared to the rest of the province, and the lower oxygen levels at those higher elevated regions may adversely impact the blood oxygen level in COVID-19 patients and increase their need for supplemental oxygen. Yet, people living in central and south areas are from lower socio-economic status which increases their risk of death when infected with SARS-CoV-2 [25]. Smoking revealed a protective effect against both low blood oxygen saturation level and death in patients with COVID-19. Studies conducted early in the pandemic have reported more severe conditions for smokers with SARS-CoV-2 infection. However, the majority have not considered the important confounders such as age, sex, and existing comorbidities. More recent evidence has shown lower infection rates in smokers and the protective effect of nicotine agent is getting more attention in the literature [26,27,28]. Having a positive history for opioids dependency was a positive predictor for low SpO2 levels. Yet, its association with COVID-19 related death was insignificant. Similar findings were reported in a study conducted in Spain, however further studies are needed to elucidate the prognosis of patients with COVID-19 who use opioids [28]. Patients with positive history of exposure to SARS-CoV-2 were more likely to develop low blood oxygen levels, but were less likely to develop severe health outcome. Additional work is recommended since studies have shown inconsistent findings in this respect, nevertheless it could be explained by the differences in the load of virus between the two groups [29, 30].
With respect to the comorbidities associated with COVID-19 health outcome, our results revealed that patients with diabetes and cardiovascular diseases have lower odds of developing low SpO2 levels, and that the two underlying diseases were insignificantly associated with COVID-19 death. Hypertension was a positive predictor of low blood oxygen levels, but it was not correlated with death in patients with SARS-CoV-2 infection. These findings do not seem to confirm previous results which have reported these underlying diseases as important contributors of poor prognosis in patients with COVID-19. However, our results seem to be defensible since most studies have only referred to hospitalized patients [28, 31]. Asthma was insignificantly associated with SpO2, but was associated with lower risk of death in COVID-19 infected patients. This is in good agreement with a study performed in United States including both in- and out-patients [32]. However, the presence of other chronic respiratory diseases was associated with both low SpO2 levels and death. Though, there was a negative association between having a history of chronic kidney disease and developing low blood oxygen level, the condition was an independent risk marker for death in patients with COVID-19. Cancer, Chronic liver disease, chronic neurological disorders, and HIV/AIDS infection were insignificantly correlated with low SpO2 levels, nevertheless, they were positively correlated with the mortality due to COVID-19. Immune deficiency disorders other than HIV/AIDS infection and chronic haematological diseases showed no relation with blood oxygen levels or death in SARS-CoV-2 infected patients in our study.
Regarding clinical presentations, fever, difficulty breathing, and impaired consciousness were important risk factors for low blood oxygen saturation level and death. On the other hand, muscle ache, and headache were important protective factors for both conditions. Cough was insignificantly associated with SpO2 levels, but patients with cough had lower risk of death due to the disease. These results corroborate previous findings [6, 28]. Nausea was insignificantly correlated with blood oxygen saturation level, but was negatively associated with mortality. Patients reporting diarrhea had lower odds of developing low blood oxygen levels, but its association with death was not significant. The presence of skin lesions was an adverse predictor for low SpO2 level, but not a significant predictor for death. Our result supports findings from a recent review on this topic, however, the association of cutaneous manifestations and death was reported as significant in the mentioned review article [33].
Finally, our study was relied on secondary analysis of existing data, hence evaluation of factors associated with the health outcomes of patients with COVID-19 were limited to available information. Given the cross-sectional nature of our study drawing conclusions about causal relationships should be done with cautious. As is the issue with most datasets on COVID-19, asymptomatic or mild cases who have not visited the healthcare facilities during the study period were not included in the analyses. Moreover, evaluation of misdiagnosis which was dependent on the sensitivity and specificity of the tests, was not possible with existing data. However, the strength of our study lies in its large multicentre study population which results in more reliable extension of inferences to the target population. Additionally, the registry from where the data was extracted, was the most complete online source of data on COVID-19 patients in the province of Tehran including all patients who have visited the public and private health care facilities in the province and were diagnosed with the disease. Given that the data was collected by trained health care professionals and based on a unified reporting online form, a high-quality data was made available to the researchers allowing real-time processing and analysis of the information.
