In the present study, clinical manifestations and laboratory findings of patients with confirmed COVID-19 were investigated in a city in Iran (Dezful). In this regard, many studies have been conducted in different parts of the world. Results of the present study revealed a statistically significant relationship between age and severe outcome, i.e., ICU admission or death (P = 0.001). Many studies performed in different parts of the world have reported similar results regarding the high prevalence of COVID-19 in elderly patients (
12-
14,
21-
23) and the relationship between age and death related covid-19 (
24).
Unlike younger people, elderly people are at a higher risk of infection with COVID-19 due to their weaker immune systems. Also, they often have chronic underlying diseases and more severe infections; consequently, the mortality rate is higher among them (
25).
This increased risk is due to several age-related biological, clinical reasons, and environmental effects, all of which cause changes in the immune system, including changes in cytokine response to immune activators, changes from (cell-mediated) type 1 cytokine response to (humoral-mediated) type 2 cytokine response with the increase in age as well as expression of chronic pro-inflammatory cytokines, which is partly due to the increased presence of old cells, as well as disruption of phagocytosis by macrophages and dendritic cells, and a change in toll-like receptor (TLR) (
26).
On the other hand, findings have indicated that the elderly are unable to take measures, such as isolating themselves and are weak at adhering to preventive measures, especially using face masks in outdoor places. These behaviors become important when social distance is not observed (
27).
Despite all these studies, some studies have reported conflicting results. Contrary to the results of our study, the results of another study have demonstrated that the COVID-19 epidemic affected more young people in the United States during June - August than in January - May 2020 (
28).
There was also a similar age change in Europe, where the average age of COVID-19 cases decreased from 54 years of age during January - May to 39 years of age during June - July, when people aged between 20 - 29 years old accounted for the highest proportion of cases (19.5%) (
29,
30).
Results of the present study showed no statistically significant relationship between sex and severe outcomes in the subjects under study consisting of 53.6% of males and 46.4% of females (P = 0.784). However, many studies have reported that being male is associated with experiencing severe disease outcomes (
13,
18,
23,
31,
32).
Although some studies showed women are more immune to viral infections (
33), but the results of our study did not show a statistically significant difference between gender and disease outcomes.
Our study's first underlying disease was cardiovascular disease (27%). Numerous studies have investigated the effects of heart disease. The pre-existing cardiovascular disease seems to be associated with severe outcomes and an increased risk of death among patients with COVID-19. Findings from our study and several others can confirm that COVID-19 is more likely to cause myocardial damage through inflammation, resulting in cardiac dysfunction and life-threatening arrhythmias (
28,
34), acute coronary syndrome, and venous thromboembolism. Potential drug-disease interactions influencing patients with COVID-19 and associated cardiovascular diseases have also become a serious concern (
28).
In the present study, diabetes (13.4%) was the second underlying disease associated with severe outcomes. In addition to circulatory diseases, endocrine diseases, such as diabetes, were also commonly seen among patients with COVID-19. Patients with comorbidities suffered from a more severe COVID-19 outcome than those with no comorbidities. In this study, kidney diseases, malignancies, and pregnancy were also mentioned, which can be due to the large sample size (
18).
However, the association between different underlying diseases and prognosis was less consistent in some studies on the coronavirus family. For example, studies evaluated the relationship between heart disease and poor clinical outcomes in influenza, SARS-CoV, or MERS-CoV have reported no definite result, or there was no disease, except for diabetes, predicting poor clinical outcomes in patients with MERS-CoV infection (
11,
18,
25,
35-
38). Our results showed a positive and significant association between cerebrovascular disease and the severe outcome of COVID-19 with less frequency (2.5%).
The presence of underlying diseases, such as cerebrovascular damage, may increase the severity of infectious diseases, which is true for COVID-19 due to its pathomechanisms (
39,
40).
Herein, a positive and significant association was also found between respiratory disease and severe outcomes of COVID-19 with less frequency (0.63%). The effect of comorbidities, including respiratory disease, has also been reported in a similar study (P = 0.0007). According to the results of this study, underlying diseases, including respiratory disease, were compared in surviving patients and those who died from COVID-19. The results showed a significant relationship between both groups, which was significantly higher in deceased patients (
23).
In a study on symptoms in patients, a similar number of symptoms were reported in inpatients and outpatients, and the most common symptoms were fever (68%), cough (69%), dyspnea (72%), chills (60%), fatigue (65%), and body ache (56%). In our study, the most common symptoms included dry cough (95%), fever (93%), and dyspnea (67%), respectively. According to the report in this study, the inpatients described dyspnea and frequent respiratory problems (P < 0.001). However, our findings revealed a significant relationship between fever, chills, nausea, and severe outcomes (
38). But perhaps what is more important in presenting these results is the duration of the fever, which was not considered in our study. In a systematic review and meta-analysis of clinical manifestations, risks, and outcomes of COVID-19, abdominal pain was introduced as a rare symptom significantly associated with severe COVID-19; thus, those with abdominal pain were controlled as soon as possible. However, abdominal pain was not reported by patients in the present study. In that systematic review study, gastrointestinal involvement (nausea, vomiting, and abdominal pain) and respiratory symptoms (dyspnea and chest pain) were associated with severe COVID-19 outcomes. In our study, nausea was also one of the symptoms associated with severe outcomes of the disease; however, among other features in our study, instead of respiratory symptoms, there was a significant association between fever, chills, and nausea with severe outcomes of the disease.
In the present study, in the baseline laboratory test results, increments and decrements were observed in WBC, MCH, HB, RDW, PLT, BUN, CR, SGOT, and SGPT in different patients. Also, there was a decrement trend in experimental values of HCT, RBC, and MCHC and an increment trend in ESR and LDH. MCV was normal in all patients. There was a statistically significant relationship between HB, RDW, PLT, BUN, CR, and LDH and severe outcomes (death and ICU admission). Also, changes in blood test results in the first three sessions were evaluated, and the results showed significant changes in the laboratory findings of WBC, MCV, MCHC, HB, PLT, CRP, ESR, BUN, CR, LDH, and SGPT between the first to third sessions. Other studies have also investigated the laboratory findings of COVID-19. For example, results of another study showed higher levels of CRP among the elderly in patients with chronic underlying diseases, especially cardiovascular diseases, and levels of WBC, neutrophils, and lymphocytes were lower in these patients than in other patients (
22).
In other studies, high levels of LDH were reported to be significantly associated with severe COVID-19 outcomes. Survival analysis also showed that high leukocytosis and LDH levels were associated with a higher mortality rate in patients with severe COVID-19 outcomes (
41). High LDH levels in severe COVID-19 cases may indicate an association between LDH and lung and tissue damage (
42,
43). Increased LDH indicates cell death and injury and is associated with a poor host immune response, resulting in higher susceptibility to severe viral infections (
42,
44,
45).
Other studies, like the present study, have also shown that some common laboratory biomarkers, which exceeded the reference range, were associated with more severe disease. Reviewing the results of these studies demonstrated significant differences between patients with mild and very severe COVID-19 outcomes in terms of leukocyte count, lymphocyte count, total protein, total bilirubin, LDH, BUN, D-dimer, CRP, and ferritin (
43).
However, it should be noted that these biomarkers are not all specific to SARS-CoV-2. However, the increased level of inflammatory biomarkers, such as CRP and ESR, indicates that the pathogenesis of the very severe SARS-CoV-2 infection is associated with the impaired inflammatory response (
18). However, some other studies have reported an increase in WBC count and a decrease in lymphocytes and platelet count in patients with severe and deadly diseases compared to those with non-severe diseases. Studies have also reported increased ALT, AST, BUN, CR, and coagulation test levels in patients with severe and deadly COVID-19 (
32,
46).
In our study, the highest respiratory support was supplied by face masks (74.5%), followed by nasal cannulas (3.4%). Another study investigated the clinical manifestations of adult inpatients with COVID-19 in a healthcare system in California (USA). Results showed that most patients received oxygen therapy through a cannula or face mask (
2).
In the present study, the mean ± SD of hospital stay was equal to 8 ± 2 days. The Mann-Whitney U test results also showed no significant difference between the two groups of patients with severe outcomes (ICU-hospitalized or dead patients) with other patients regarding the average length of hospital stay. However, results of a study conducted in China reported a mean hospital stay of 24 days for all the patients (range = 5 - 50 days), 36 days for critically ill patients, and 18 days for non-critically ill patients (
47). This discrepancy between the results of the studies may be attributed to the patients҆ consciousness, early referrals, and conditions governing the society regarding COVID-19 pandemic policymaking and management in China (
36). There is a relationship between the spread of the virus and different variables in different geographical areas. Therefore, various variables can be analyzed in the future challenges; for example, the date when the first COVID-19 case was identified in the country and studying humidity, temperature, and other meteorological variables, as well as other types of variables in different regions, such as cultural behavior, religious behavior, healthcare-related habits, eating habits, etc., which may influence the incidence or severity of the disease (
48).
5.1. Conclusions
Covid-19 has rapidly spread and often progresses among people. In the world, we have encountered limited ICU units and a limitation of hospital beds; thus, using some factors, such as clinical manifestation and laboratory tests, gives an early warning for rapid interventions and decreases the number of deaths and ICU admissions of these patients. So, considering the main symptoms of COVID-19, such as fever, cough, fatigue, and dyspnea, can have a key role in the early detection of this disease. However, the data from this study should be interpreted with caution.