DOI: https://doi.org/10.21203/rs.3.rs-140018/v1
Background: Coronavirus disease highly contagious, is prevalent in all age and sex groups infecting the respiratory system. The present study seeks to investigate the epidemiology and effective factors in mortality of patients with COVID-19 in Ardabil province, northwestern of Iran.
Methods: In a retrospective study, the hospitalized patients with laboratory diagnosed COVID-19 between February to August, 2020 were enrolled. Data registration portal was designated according to WHO recommendation. In this portal, demographic information, clinical presentation, laboratorial and imaging data were registered for patients in all hospitals in the same format. The Hosmer-Lemeshow guideline was used for variable selection in a multiple model.
Results: Of the patients involved 2812(50.3%) were male and 150 (2.7%) had a contact with a confirmed case of COVID-19 in the last 14 days. Pre-existing morbidity was reported in 1310 (23.4%) patients. Of all patients 477(8.5%) died due to COVID 19. The hospitalization in ICU had significant correlation with fever or chills, shortness of breath, aches and pains, runny nose and chest pain.
Conclusions: Hospitalization had the strongest effect on mortality followed by hospitalization in ICU, and higher age. This study showed that having some symptoms like aches and pains and headache can serve as preventive factors of mortality.
Coronavirus is a group of single- stranded, enveloped RNA virus with a diameter of 120–180 nm and is divided into four groups: Alpha, Beta, Gamma and Delta. COVID-19 is a member of the Bete-coronavirus family[1, 2].This type of virus is highly contagious and infects the respiratory system. Direct contact and respiratory droplets are the most common way of transmitting the virus in the community but other ways have also been suggested [3]. Covid-19 is associated with the demographic situation of the community. The disease is prevalent in all age and sex groups, but the highest mortality is in older men with an average age of 75 years who have a history of diseases such as cardiovascular diseases, diabetes, high blood pressure, chronic respiratory diseases, cancer or previous surgery [4, 5]. According to the World Health Organization's (WHO) weekly report, as of October 4, 2020, there have been 35,347,404 confirmed cases of the disease of which 1,039,406 were mortality rate the highest number of it reported at 208,433 and 103,569 in the United States and India[6]. According to various studies, 18 to 33% of patients admitted to the hospital need mechanical ventilation, and up to 20% of patients are admitted to the ICU [7–10]. The most common symptoms of the disease include fever, cough, shortness of breath, fatigue and muscle pain that are observed in most patients and other symptoms such as diarrhea, headache and nausea have also been reported with a low percentage [11, 12]. Given that that no vaccine has been successfully developed to prevent COVID-19 to date, public health measures to control the infection are necessary to limit the global spread of the virus to reduce the incidence of COVID-19. It is essential to limit travel, human-to-human transmission in order to reduce secondary infections in close contact with health care personnel and to prevent further spread of the disease. Many efforts have been made to slow the progression of the disease in order to provide or buy time for better public health care systems, better description of COVID − 19 to guide public health advice and timely development of diagnosis, treatment and vaccines[13–15]. However, in some countries such as Iran, the death toll is still alarmingly high. The aim of this study is to investigate the epidemiology and effective factors in mortality of patients with COVID-19 in Ardabil province, northwestern of Iran so that by identifying these factors we can provide basic proceedings for its control and prevention.
This retrospective cohort study was performed on 5587 patients in Ardabil, northwest of Iran. All patients who were admitted in the hospitals of Ardabil province from February to August 2020 were recruited in the study. During this pandemic, ten hospitals were allocated for COVID- 19 in Ardabil province. All needed data were registered in the COVID-19 case registration portal at Ardabil University of Medical Sciences. The data were obtained retrospectively from this portal. Data registration portal was designated according to WHO recommendation. In this portal, demographic information, clinical presentation, laboratorial and imaging data was registered for patients in all hospitals in the same format.
The patients who were diagnosed with the COVID-19 according to WHO guidelines has been registered in the mentioned portal. The outcome was defined as death (non-survivor) or discharge (survivor). The criteria for discharge were the improvement of the general status and respiratory symptoms, absence of fever for at least 3 days, chest CT scan improvement in both lungs, and at least one-time throat-swab or nasal-swap samples negative for SARS-CoV RNA assessment.
To perform simple statistical analysis, Chi square and Fisher’s exact test was used to evaluate the relationship among hospitalization, hospitalized in the ICU, and outcome of disease with the related factors. Univariate and multiple logistic regression models were run to examine the correlation among different variables and death due to COVID-19. The Hosmer-Lemeshow guidelines were used for variable selection in a multiple model[16]. Alpha level (p) for determining statistically significant differences was set at 0.5.
The number of all registered patient were 5586. This study indicated that the mean age of the patients was indicates 52.25 ± 20.21 years. Of all patients, 2812(50.3%) were male and 150 (2.7%) had a contact with a confirmed case of COVID-19 in the last 14 days. Pre-existing morbidity was reported in 1310 (23.4%) patients. Of all patients 477(8.5%) of them died due to COVID-19.
Table 1 shows frequency of demographic characteristics and related factors to hospitalization, hospitalization in ICU and the outcome of the disease. As seen in table, hospitalization and the outcome of the disease had significant correlation with all studies variables (p < 0.05). Hospitalization in ICU was significantly was correlated with age, co morbidity, the outcome of the disease, and abnormal findings in chest radiography. However, hospitalization in ICU didn’t have a significant correlation with sex and previous contact with a confirmed case of COVID-19 (p > 0.05).
Items |
Hospitalization |
Hospitalization in ICU |
Outcome |
||||
Yes (%) |
P value |
Yes (%) |
P value |
Survive |
Non survive |
P value |
|
|
|
N(%) |
N(%) |
||||
Total |
N=4188 |
|
N=124 |
|
N=5110 |
N=477 |
|
Age groups |
|
|
|
|
|
|
|
Under 50 |
1509(36.0) |
<0.001 |
37(29.8) |
0.001 |
2432(47.6) |
79(16.6) |
<0.001 |
50 and higher |
2679(64.0) |
|
87(70.2) |
|
2678(52.4) |
398(83.4) |
|
Sex |
|
|
|
|
|
|
|
Male |
2017(48.2) |
<0.001 |
52(41.9) |
0.082 |
2570(50.3) |
205(43.0) |
0.002 |
Female |
2171(51.8) |
|
72(58.1) |
|
2540(49.7) |
272(57.0) |
|
Co morbidity |
|
|
|
|
|
|
|
No |
3025(72.2) |
<0.001 |
77(62.1) |
<0.001 |
3962(77.5) |
315(66.0) |
<0.001 |
Yes |
1163(27.8) |
|
47(37.9) |
|
1148(22.5) |
162(34.0) |
|
Outcome |
|
|
|
|
|
|
|
Survive |
3725(88.9) |
<0.001 |
72(58.1) |
<0.001 |
-- |
-- |
-- |
Non survive |
463(11.1) |
|
52(41.9) |
|
-- |
-- |
|
Having contact with a confirmed case of COVID 19 in last 14 days |
|
|
|
|
|
|
|
No |
4042(98.3) |
<0.001 |
115(96.6) |
0.568 |
148(3.0) |
2(0.4) |
0.001 |
Yes |
68(1.7) |
|
4(3.4) |
|
4863(97.0) |
470(99.6) |
|
Abnormal findings in chest radiography |
|
|
|
|
|
|
|
No |
3676(87.8) |
<0.001 |
103(83.1) |
0.005 |
4641(90.8) |
413(86.6) |
0.003 |
Yes |
512(12.2) |
|
21(16.9) |
|
469(9.2) |
64(13.4) |
|
The distribution of hospitalization, hospitalization in ICU and the outcome of the disease by clinical presentation are illustrated in Table 2. As indicated in Table 2 hospitalization have a significant correlation with all symptoms (except diarrhea). This table also shows that hospitalization in ICU have significant correlation with fever or chills, shortness of breath, aches and pains, runny nose and chest pain. This table revealed that outcome of disease has significant correlation with all symptoms except cough and sore throat.
Items |
Hospitalization |
Hospitalization in ICU |
Outcome |
||||
---|---|---|---|---|---|---|---|
Yes (%) |
P value |
Yes (%) |
P value |
Survive |
Non survive |
P value |
|
N = 4188 |
N = 124 |
N = 5110 |
N = 477 |
||||
Fever or chills |
|||||||
No |
1732(41.4) |
< 0.001 |
46(37.1) |
0.040 |
2432(47.6) |
148(31.0) |
< 0.001 |
Yes |
2456(58.6) |
78(62.9) |
2678(52.4) |
329(69.0) |
|||
Cough |
|||||||
No |
1059(25.3) |
< 0.001 |
41(33.1) |
0.137 |
1406(27.5) |
114(23.9) |
0.090 |
Yes |
3129(74.7) |
83(66.9) |
3704(72.5) |
363(76.1) |
|||
Shortness of breath |
|||||||
No |
1561(37.3) |
< 0.001 |
24(19.4) |
< 0.001 |
2299(45.0) |
108(22.6) |
< 0.001 |
Yes |
2627(62.7) |
100(80.6) |
2811(55.0) |
369(77.4) |
|||
Aches and pains |
|||||||
No |
2844(67.9) |
< 0.001 |
96(77.4) |
0.007 |
3339(65.3) |
352(73.8) |
< 0.001 |
Yes |
1344(32.1) |
28(22.6) |
1771(34.7) |
125(26.2) |
|||
Sore throat |
|||||||
No |
2463(58.8) |
< 0.001 |
69(55.6) |
0.712 |
2938(57.5) |
262(54.9) |
0.278 |
Yes |
1725(41.2) |
55(44.4) |
2172(42.5) |
215(45.1) |
|||
Headache |
|||||||
No |
3460(82.6) |
< 0.001 |
109(87.9) |
0.055 |
4120(80.6) |
419(87.8) |
< 0.001 |
Yes |
728(17.4) |
15(12.1) |
990(19.4) |
58(12.2) |
|||
Runny nose |
|||||||
No |
3964(94.5) |
0.006 |
110(88.7) |
0.001 |
4885(95.6) |
429(89.9) |
< 0.001 |
Yes |
224(5.3) |
14(11.3) |
225(4.4) |
48(10.1) |
|||
Diarrhea |
|||||||
No |
4018(95.9) |
0.130 |
120(96.8) |
0.552 |
4881(95.5) |
466(97.7) |
0.025 |
Yes |
170(4.1) |
4(3.2) |
229(4.5) |
11(2.3) |
|||
Chest pain |
|||||||
No |
3870(92.4) |
< 0.001 |
95(76.6) |
< 0.001 |
4792(93.8) |
413(86.6) |
< 0.001 |
Yes |
318(7.6) |
29(23.4) |
318(6.2) |
64(13.4) |
In the univariate analysis, all possible effective factors were interred to the model. As can be seen in Table 3, older patients had higher odds of death. In addition, except having cough and sore throat, all other variables were related to death. This analysis indicated that having contact with a confirmed case of COVID-19 in last 14 days, aches and pains, headache and diarrhea have protective effect on death but other variables increase the odds of death.
Death due to COVID 19 |
||||||
---|---|---|---|---|---|---|
Crude estimation |
Adjusted estimation |
|||||
Variables |
OR |
95%CI |
P |
OR |
95%CI |
P |
Age (50 years old or higher) |
4.57 |
3.57–5.86 |
< 0.001 |
3.11 |
2.39–4.06 |
< 0.001 |
Sex (being male) |
1.34 |
1.11–1.62 |
0.002 |
1.20 |
0.98–1.47 |
0.072 |
Co-morbidity |
1.77 |
1.45–2.17 |
< 0.001 |
1.25 |
1.00-1.56 |
0.055 |
Having contact with a confirmed case of COVID 19 in last 14 days |
0.14 |
0.03–0.57 |
0.006 |
0.290 |
0.07–1.22 |
0.091 |
Having abnormal findings in chest radiography |
1.53 |
1.16–2.03 |
0.003 |
1.00 |
0.74–1.35 |
0.996 |
Fever or chills |
2.02 |
1.65–2.47 |
< 0.001 |
1.61 |
1.29–2.02 |
< 0.001 |
Cough |
1.21 |
0.97–1.50 |
0.090 |
0.91 |
0.71–1.17 |
0.463 |
Shortness of breath |
2.79 |
2.24–3.49 |
< 0.001 |
1.82 |
1.44–2.31 |
< 0.001 |
Aches and pains |
0.67 |
0.54–0.83 |
< 0.001 |
0.71 |
0.57–0.89 |
0.003 |
Sore throat |
1.11 |
0.92–1.34 |
0.278 |
-- |
-- |
-- |
Headache |
0.58 |
0.43–0.76 |
< 0.001 |
0.64 |
0.47–0.86 |
0.004 |
Runny nose |
2.43 |
1.75–3.37 |
< 0.001 |
1.54 |
1.06–2.24 |
0.022 |
Diarrhea |
0.50 |
0.27–0.93 |
0.028 |
0.66 |
0.35–1.26 |
0.206 |
Chest pain |
2.33 |
1.75–3.11 |
< 0.001 |
1.53 |
1.10–2.13 |
0.011 |
Hospitalization |
12.28 |
7.19–20.99 |
< 0.001 |
5.66 |
3.28–9.78 |
< 0.001 |
Hospitalization in ICU |
8.56 |
5.91–12.39 |
< 0.001 |
5.12 |
3.40–7.71 |
< 0.001 |
However, the result of multiple logistic regression model indicated that after adjusting for other factors, higher age (OR = 3.11), fever or chills (OR = 1.61), shortness of breath (OR = 1.82), aches and pains (OR = 0.71), headache (OR = 0.64), runny nose (OR = 1.54), chest pain (OR = 1.53), hospitalization (OR = 5.66), and hospitalization in ICU (OR = 5.12) were associated with death. In other word, among these related factors, having headache and aches and pains decreased the odds of death. However other factors are related with increased odds of death due to COVID-19 in all patients.
In this study we reported the characteristics of all patients with COVID 19 in Ardebil province in the northwest of Iran. The clinical characteristics of these patients showed that the age (50-year-old and higher), hospitalization and hospitalization in ICU were the most important risk factors for death.
The present study also indicated that there is no gender difference in the prevalence of COVID-19 (49.7% in females vs. 50.3% in males). However, of deceased patients 43% was male. Some studies have reported greater prevalence of COVID-19 in males[17–19]. A study conducted in Iran showed that males are in higher risk of mortality[20]. But, gender differences seems to have less importance as a prognostic factor for death compased with age [19]. Some studies also have indicated that the susceptibility of older males is higher than older females[21]. Anyway, in this study male gender didn’t have significant effect on death of patients in final adjusted regression logistic model.
Several studies have indicated that comorbidities are one the strongest predictors of death or sever COVID-19[22–24]. Another study from Iran showed that having comorbidities had a significant effect on mortality [20]. Our findings showed that having any comorbidity was associated with hospitalization, hospitalization in ICU and outcome of disease. Also, in univariate analysis comorbidity increased the odds of death. However, this association didn’t remain significant in the final model. Further investigations are needed to assess the role of comorbidities on the mortality of COVID 19 in Iran.
Cough was to be the most common (74.7%) symptom among hospitalized patients followed by shortness of breath (62.7%). Of symptoms of the disease, we found that fever or chills, shortness of breath, aches and pains, headache, runny nose, diarrhea and chest pain were factors independently associated with mortality when adjusted for other variables. Among these symptoms, shortness of breath had the strongest effect on death (OR = 2.79). Some studies reported other frequencies for disease symptoms. For example among Italian and Spanish patients fever was reported as the most common symptom[19, 25]. Probably there are complex interactions between symptoms of COVID 19 and other independent variables like age and gender. Identifying such a complex relationship among independent variables may help to determine the portion of each symptom in death.
Our findings revealed that hospitalizing (OR = 12.28) and hospitalization in ICU (OR = 5.56) increased the odds of death among all patients. In line with our results, a study from Mexico reported that hospitalization (OR = 5.02) and hospitalization in ICU (OR = 1.79) were associated with death[26]. This could happen due to condition of patients at admission time. Patients with severe and critical conditions are more likely to hospitalized or hospitalized in ICU, resulting in a high in hospital mortality.
This study revealed that most of COVID-19 deceased patients were older than 50 years old. Hospitalization had the strongest effect on mortality followed by hospitalization in ICU, and higher age. This study showed that having some symptoms like aches and pains and headache can serve as preventive factors from mortality. Because of limitations in treatment and lack of medicines, proper prioritization considering risk and protective factors is very important in decreasing mortality rates.
The authors thank Ardabil Health Central and all hospitals Stoff for enabling this study.
AAG and EMA: Study design, Data analysis, Writing - original draft, Writing - review & editing. DA, HG and SHA: Data analysis, Writing - review & editing. EMA and AAG: Data collection
This research was supported by a grant from Ardabil University of Medical Sciences (project No: 3899).
The study was approved by the Ethics Committee of Ardabil University of Medical Sciences (IR.ARUMS.REC.1399.096). Permission to conduct the study was obtained from this committee.
Not applicable.
The authors declare no conflict of interest.