In-Hospital Death Due to COVID-19 Disease in Iranian Patients: A Systematic Review and Meta-Analysis Study

Context: The prevalence of in-hospital death due to COVID-19 hospital is one of the qualitative indexes, which can be used to assess the quality of care, as well as the mortality patterns in COVID-19 pandemic. Objectives: Therefore, this systematic and meta-analysis study has been done with the aim of estimating overall prevalence in-hospital death due to COVID-19 disease in iranian patients Evidence Acquisition: Articles were identied through international searching databases including PubMed, Scopus, Elsevier, Google Scholar, and Web of Science and Iranian scientic information database (SID), Health.barakatkns, IranDoc, Civilica and MagIran. We reviewed systematically all studies reporting the prevalence of in-hospital death due to COVID-19 disease. In this study meta-analysis method with random effect model has been used to estimate the pooled prevalence. Results: 118 records were identied by the electronic search, of which 43 studies were identied as relevant papers that were meta-analyzed for the pooled in-hospital death due to COVID-19 prevalence. Overall, prevalence of death were 12.16% (95% CI: 10.72%-13.61%). The highest and lowest death prevalence has been reported in Northern Provinces (Gilan, 27.27% (95% CI: 8.66%-45.88%) and Mazandaran, 21.27% (95% CI: 18.14%-24.40%)) and Turkish-speaking provinces (Azerbaijan, East, 3.29% (95% CI: 2.11%-4.47%) and Zanjan, 3.42% (95% CI: 1.82%-5.02%)) respectively. Conclusions: Considering the death rate obtained in this study and its comparison with other countries, it can be said that the performance of the Iranian medical system in COVID-19 pandemic is acceptable.


Context
In late 2019 began a wave of respiratory diseases in Wuhan(China) On March 11, 2020, according to the World Health Organization, the COVID-19 pandemic was announced [1].
The World Health Organisation estimates that 14% of infected cases are severe and require hospitalization and 4% of infected die [2]. Approximately, 143 million con rmed cases and more than 3 million deaths were reported by the World Health Organization (WHO) as of April 20, 2021 [3].
COVID-19 poses a signi cant global threat due to the lack of a validated cure and the di culty of its delivery [4]. The rate of death due to COVID-19 in each country depends on the actual number of cases, screening system, the capacity of the health and management [5][6][7]. COVID-19 patients had a very high ranging in-hospital death rate of admitted patients. The large cohort study in China ((9.6%)[8], 3.98% [9]), USA (8.2% [10], 18.58% [11], 45.11% [12], 22.77% [13]), Brazil (26.82% [14], Spain (21.3% [15], 20.90%[16], 21.41% [17]), France (16.87% [18], 27.72% [19]), Italy (28% [20]) reported various prevalence of in-hospital death due to COVID-19. Abate et al in a meta analysis study showed that the pooled prevalence of inhospital mortality in patients with coronavirus disease was 15% (95% CI: 13 to 17) [21]. in-hospital death is one of the qualitative indexes, which can be used to assess the resilience of a health system in Crisis situations. However, the study of in-hospital death due to Covid-19 in Iran is of great importance for two reasons. First, Iran was one of the rst countries to face the COVID-19, and on the other hand, due to the existence of many sanctions, this country has not been able to access many equipment and medicines.

Objectives
Therefore, this systematic and meta-analysis study has been done with the aim of estimating overall prevalence in-hospital death due to COVID-19 disease in iranian patients.

Search Strategy
In this systematic review and meta-analysis study, All studies that reported in-hospital death in admitted patients to hospital due to COVID-19 has been used. The literature in Iran was acquired through Iranian scienti c data base including SID, IranDoc, Health.barakatkns, MagIran and Civilica and international searching databases including PubMed, Scopus, Elsevier and Web of Science. Additional search was also done by Google Scholar search engine.
The last search took place on 11 April 2021. To search and include related studies as many as possible, we used the following terms: "Deceased", "Mortality", "Death", "COVID 19"," Cross sectional","Cohort"," Observational","Iran"(or the names of its provinces), as keywords for titles and/or abstracts in MeSH word

Selection of Studies and Data Extraction
Published studies were regarded as quali ed for the analysis if they met the following criteria: (1) Observational, cross-sectional or cohort studies with the full text of the paper available in the Persian or English languages, (2) studies with a sample size of more than 30, and (3) studies reporting the prevalence of in-hospital death in admitted patients to hospital due to COVID-19, (4) studies with mean Age ranges from 16 to 100, (5) studies with approved diagnosis of COVID-19 by means positive RT-PCR of throat-swab specimens or the chest CT scans according to the WHO interim guidance including ground glass opacity in addition to ill-de ned margins, smooth or irregular interlobular septal thickening, air bronchogram, crazy-paving pattern, and thickening the adjacent pleura [22][23][24] conversely, the following studies were excluded: (1) non-English or non-Persian full-text reports, (2) studies not providing enough data to estimate the death prevalence, (3) studies designed as letters to the editor, expert opinions, editorials, commentaries, case-reports, case-series, and reviews, and (4) Studies reporting overlapping data.

Data Extraction
All articles categorized as potentially relevant were reviewed separately by both of the authors (Seyed Hassan Saadat and Alireza Najimi-Varzaneh), In case of inconsistency in the results of the two authors, the other two authors ((Mostafa Ghanei and Mohammad Gholami Fesharaki ) review the articles and nally the results of the articles summarized the following data using Excel datasheets: First author's name, duration of study, number of COVID-19 hospitalation patients, study sample size, name of the province, mean age and gender of responders. The analysis was conducted according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) [25]. In this study, The "Newcastle Ottawa Scale (NOS)" was used to evaluate the accuracy of the data in this analysis.

Statistical Analysis
The prevalence of in-hospitalized death among COVID-19 patient from each province of Iran was computed by metan command. Statistical tests of heterogeneity among the studies were carried out using the Q test (P < 0.10 indicates statistically signi cant heterogeneity) and I-squared statistics. We also used a funnel plot to investigate publication bias. In this study, "metafor" package in R software version 3.6. In this study, the publication bias was assessed graphically and statistically by funnel plot, and based on visual inspection of the funnel plot, Begg's Test, and Egger's test.

Search Results and Study Selection
The study selection process is presented in Figure 1. A total of 118 studies were potentially associated with study subject. After reviewing the abstracts and titles, 79 studies were eliminated based on the stated inclusion and exclusion criteria. After the full text screening and quality assessment, a total of 43 records were deemed as eligible studies published until 11 April 2021.

Evaluating Heterogeneity Index and Publication Bias
In this study, for evaluating heterogeneity and publication bias the I-squared statistics and Begg and Egger tests has been used respectively. If the I-squared were upper 40% it showed heterogeneity and the random effect model must be used. In this study I-squared calculated 97.3%. Therefore in this study random model has been used. In addition, the upper 5% of Begg's (T=0.10, P-value=0.920) and Egger's Test (T=1.90, P-value=0.051) P-value showed any publication bias in this study 4.3. Prevalence of in-hospital death due to COVID-19 in Iran country Data, including the prevalence of in-hospital death due to COVID-19 as well as other features like reference, province, rst author's name, study sample size, mean age and male percent were presented in Table1. Also, the pooled prevalence of in-hospital death due to COVID-19 according to the provinces of Iran were presented in Table 2 . in this study from 43 study, totally 67928 patients evaluated that from them 6781 death has been reported.

Discussion
Our meta-analysis study of 43 published articles involving 67928 patients is provide a comprehensive analysis of in-hospital death due to COVID-19 disease. The pooled overall, prevalence of in-hospital death in Iran country is 12.16% (95% CI: 10.72%-13.61%). This estimation is upper than large cohort study that reported in-hospital death due to COVID-19 in China [8,9] and lower than study reported in in-hospital mortality in USA [11][12][13], Brazil [14], Spain [15][16][17], France [18,19] and Italy [20]. This prevalance is also lower than pooled meta prevalence of in-hospital mortality in patients with COVID-19 in the world [21].
This result can be justi ed by the fact that these provinces are two destination of tourists travelers in Iran and the main reason for this high prevalence is travel. Previous studies has been identi ed that travel is a major risk factor for spread . Increaseing prevalence of disease leads to increasing severity and increasing severity tend to higher prevalance in-hospital death due to COVID-19 disease.
The higher the prevalence of the disease, the greater the severity of the disease and, accordingly, the greater the death of patients. There are several limitations to be noted in the present study. Firstly, some provinces of Iran did not report any published article on in-hospital death due to COVID-19, so the generalizability of the above results to the whole of Iran is biased. Secondly, most of article that has been published in-hospital death due to COVID-19 are from Tehran city so in fact the pooled prevalence of Iran is close to the prevalence of Tehran, Furthermore, non existent data or low number of studies from certain provinces have not allowed us to report geographical distribution of Iran. Finally, due to the lack of metaanalysis studies in other countries, it is suggested that the present study be performed for other countries and the results be compared with the present study.

Conclusion
Considering the death rate obtained in this study and its comparison with other countries, it can be said that the performance of the Iranian medical system in COVID-19 pandemic is acceptable.    The Forest plot in-hospital death due to COVID-19 disease in Iranian patients