3.1| Study population
A total of 270624 patients with COVID-19 were admitted to hospitals in Tehran province between 21st March, 2021 and 3rd October, 2021. The median age of COVID-19 patients was 50 (IQR: 67, 64) years and 50.2% of patients were male. As shown in Figure 1-A, two peaks were occurred in the number of patients admitted to hospitals at the end of April and in the middle of August. These peaks were related respectively to the alpha and delta variants. Figure 1-B showed that the difference in death frequencies between the two peaks was less than the difference in admission frequencies. According to Figure 1-C, the youngest category of patients was more frequent during the second peak. As shown in Figure 1.D, the number of patients treated in ICUs and those not treated in ICUs did not differ between the first and second peaks.
Insert Figure 1
Patients’ characteristics were summarized by month of admission, as shown in Table 1 (See Supplementary Table 1, Additional File 1). Accordingly, the proportion of men was 51.9 (95% CI: 50.6, 53.2) in March, declining to 47.3 (45.2, 49.5) by October. In March, the median age was 55 (IQR: 39, 68), and in October, it fell to 48 (36, 65). In April (first peak), the proportion of patients aged younger than 40, 40-49, and 50-59 was 25.5 (95% CI: 25.1, 26.0), 16.5 (95% CI: 16.1, 16.8), and 19.1 (95% CI: 18.7, 19.5) respectively, which was increased to 31.4 (95% CI: 32.0, 32.9), 20.0 (95% CI: 19.7, 20.3), and 21.0 (95% CI: 20.7, 21.3) in August (second peak). The trend of admission proportion was reversed for those aged 60 and older; lower patients’ proportions were noted in August as compared to the April.
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3.2| Overall morality
18623 (6.88%) patients with COVID-19 died during the study period. The death proportion by ward (non-ICU and ICU treated) and patient status (survived and deceased) is presented in Table 2 (See Supplementary Table 2, Additional File 1). The death proportion was 3.2 (95 CI: 3.2-3.3) for patients admitted to non-ICU wards, while for those admitted to ICU, it was 34.0 (95 CI: 33.5-34.5). The strongest associations were observed between outcome (survived and deceased) and age (EF=0.23), hospitalization days (EF=0.21), respiratory distress (EF=0.14), number of comorbidities (EF=0.07), kidney disease (EF=0.06), chest pain (EF=0.05), hypertension (EF=0.05), and diabetes (EF=0.05).
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A multiple Cox regression was used to evaluate the adjusted risk of COVID-19 death among hospitalized patients, as shown in Figure 2 (See Supplementary Table 3, Additional File 1). Compared to patients admitted in March, those admitted in June had lower risk of COVID-19 death (HR: 0.87; 95% CI: 0.79, 0.96). However, a higher risk of COVID-19 death was observed among patients admitted to the hospital in July (HR: 1.28; 95% CI: 1.17, 1.40), August (HR: 1.40; 95% CI: 1.28, 1.52), September (HR: 1.37; 95% CI: 1.25, 1.50) and October (HR: 4.63; 95% CI2.77, 7.74). The hazard of death for men was 17% higher than for women (HR: 1.17; 95% CI: 1.14, 1.21). The risk of COVID-19 death increased by age and the highest risk of death observed in those older than 89 years of age (HR: 9.61; 95% CI: 8.81, 10.49). COVID-19 death risk was associated with higher number of comorbidities, and those with more than three comorbidities were at higher risk (HR: 1.59; 95% CI: 1.39, 1.82).
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Figure 6 showed that the highest death proportions were observed in counties including Malard (10.88%), Robat-Karim (8.81%) and Eslamshahr (8.48%). Among ICU-treated, the highest death proportions were occurred in Pishva (52.03%), Varamin (46.64%), and Pakdasht (43.26%) (See Supplementary Figure 2 and, Additional File 1).
3.3| Trend of mortality over study period
Figure 3 (See Supplementary Table 4, Additional File 1) showed the trend of mortality for total patients, ICU and non-ICU treated by month of admission. Death proportion among ICU-treated increased from March (30.8; 95% CI: 28.3, 33.4) to April (36.8; 95% CI: 35.5, 38.1), remained constant until May (35.0; 95% CI: 33.6, 36.4), and declined in January (28.0.8; 95% CI: 26.6, 29.5) during the first peak of COVID-19. On the second peak, the death proportion increased in July (35.9, 95% CI: 34.7, 37.1), then more rose to the top in August (39.8, 95% CI: 38.6, 41.1), then declined in September (26.8, 95% CI: 34.7, 37.1) and October (4.9, 95% CI: 2.6, 8.8). Among non-ICU patients, however, mortality peaked in April (4.9, 95% CI: 4.7, 5.1) and July (3.2, 95% CI: 3.4, 3.8), respectively. Furthermore, the proportion of deaths was highest during the first peak among non-ICU patients.
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The log-rank test showed the significant difference in survival rate between months. Accordingly, the survival rate in the August was significantly lower than in April (See Supplementary Table 5 and Supplementary Figure 1, Additional File 1). In addition, the risk of COVID-19 death was increased from 1.28 (95% CI: 1.15, 1.43) in July to 15.51 (95% CI: 8.50, 28.31) in August during the second peak among those admitted to the ICU. However, the highest risk of death among non-ICU patients was 1.72 (95% CI: 1.47, 2.00) in August, as shown in Figure 4 (See Supplementary Table 6, Additional File 1).
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According to Figure 5, the death proportion was illustrated over time by sex, age group, number of comorbidities and nationality. Accordingly, an overall downward trend was observed with varying magnitudes over study time.
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Nonetheless, the trend of death proportions varied from county to county in Tehran province, as shown in Figure 6. Furthermore, the death proportion among ICU patient had risen in most counties until August, but declined for patients not receiving ICU treatment (See Supplementary Figure 2 and 3, Additional File 1).
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In the next step, the subgroup analysis was presented in Figure 7. Accordingly, the month of admission had a different impact on mortality in various age groups, number of comorbidities and nationality, but there wasn't any difference in HR between males and females based on the month of admission.
Insert Figure 7