A meta-analysis of clinical characteristics and mortality COVID-19 pneumonia

doi:10.21203/rs.3.rs-18723/v2

Abstract: Objective To investigate the Corona Virus Disease 2019(COVID-19) clinical characteristics and mortality risk by pooling the open published data. Methods Studies relevant to COVID-19 published in Pubmed, China Wanfang database, ChinaXiv and medRxiv were systematic screened by using the text word of “COVID-19”, 2019-nCoV, “SARS-CoV-2”, “NCP”. The mortality and clinical characteristic of the COVID-19 cases such as male/female ratio, mechanical ventilation ratio and top c linical symptom rate of the COVID-19 cases were pooled.

Results Ten clinical studies relevant to COVID-19 were identified by electronic searching the related databases. The combined mortality was 0.03(95%CI: 0.01-0.04) for COVID-19 cases by random effect model. The pooled female ratio of the COVID-19 cases from 10 published data was 0.41(95%CI:0.37-0.46). The pooled invasive and non-invasive ventilation ratio were 0.03(95%CI:0.01-0.05) and 0.06(95%CI:0.02-0.09) respectively for patients with COVID-19 pneumonia. The pooled clinical symptom rate of fever, cough, headache and fatigue were 0.80(95%CI:0.60-1.01), 0.12(95%CI:0.08-0.17), 0.68(95%CI:0.57-0.73) and 0.51(95%CI:0.36-0.67) respectively under random effect model.

Conclusion According to the present published data, male was more cline to susceptible to COVID-19 compared to female. The fever, cough and fatigue were the most common symptom of COVID-19 cases. About 10% of patients received invasive or noninvasive mechanical ventilation with the overall crude mortality of 3%.

Infectious Diseases

Novel coronavirus pneumonia

COVID-19

mortality

mechanical ventilation

clinical symptom

meta-analysis

A novel coronavirus infection (COVID-19) was outbreak in Wuhan China at the end of 2019[1, 2]. Since 8 March, according to the reports of 31 provinces (autonomous regions, municipalities directly under the central government) and Xinjiang production and Construction Corps, there are 16145 confirmed cases in hospital (including 4492 severe cases), 61475 cumulative discharged cases, 3158 deaths, 80778 cumulative confirmed cases in China (http://www.nhc.gov.cn/). Furthermore, COVID-19 seems to have been outbreak all over the world with more than 100 countries had been discovered of COVID-19 cases[3, 4], Figure 1. Numerous studies about the clinical features of COVID-19 had been reported in the literature[5-7]. Most of the studies are retrospective clinical epidemiological analysis. However, the sample size of each individual study was small and the statistical power was limited. According to the individual study, the patients characteristics such as sex ratio, the proportion of severe patients requiring mechanical ventilation and the mortality were quite different in different studies. In order to further evaluate the clinical characteristics and mortality of COVID-19, we searched and summarized the published literature, and made the meta-analysis.

Publication searching

Studies relevant to COVID-19 were systematic electronic searched in Pubmed, China Wanfang database, ChinaXiv and medRxiv by using the text word of “COVID-19/ Corona Virus Disease 2019”, 2019-nCoV, “SARS-CoV-2” and “NCP/Novel Coronavirus Pneumonia ”. The references of the included studies were also screened in order to find the potential suitable publication.

Publication inclusion and exclusion criteria

For the initial identified studies, the publications were further screened for inclusion or exclusion by two reviewers (Shangxia Jiang and Yueming Wu) independently. The publication inclusion criteria were: 1) Studies relevant to human beings; 2) COVID-19 was diagnosed by nucleic acid assay; 3)The mortality, male/female ratio, cases received mechanical ventilation and cases of the typical clinical symptom were present in the original publications; 4) Studies were published in English or Chinese; Publication exclusion criteria were: 1) Studies about COVID-19 suspected case; 2) Not enough data such as mortality, symptom and et c can be extracted from the original publications; 3) Studies published in other language neither English nor Chinese.

Data extraction

The data of each included publication was extracted by two reviewers (Tianzheng Lou and Junlong Xu) independently and made cross check. In case of disagreement, the corresponding author was consulted for final decision. The extracted data and information were as follows: 1) The first author's name; 2) publication time; 3) source of literature; 4) number of patients in the original study; 5) source of patients (region); 6) sex ratio COVID-2019; 8) number of deaths; 9) number of patients with mechanical ventilation; 10) number of cases in each symptom.

Statistical analysis

STATA16.0 statistical software was applied for data analysis. Before pooling the results, the data was examined for statistical heterogeneity by I² test. If statistical heterogeneity existed (I²>50%, p<0.05), the data was combined through random effect model, otherwise, the data was pooled by fixed effect mode. Two tails p<0.05 was considered statistical difference.

General quality of the included 10 studies

After systematic electronic searching the databases, 10 high quality studies relevant to clinical characteristics of COVID-19 pneumonia were finally identified, Figure 2. All of the included studies are from China mainland and mainly in Wuhan Hubei City. The sample size ranged from 13 to 44672. The general characteristics of the included 10 publications were showed in Table 1.

Pooled gender distribution

All the included 10 publications had reported the gender ratio. Due to significant statistical heterogeneity, the data was pooled by random effect model. The combined female ratio of the COVID-19 cases from 10 published data was 0.41(95%CI:0.37-0.46), Figure 3.

Pooled mortality

Eight studies reported the mortality data of the COVID-19 pneumonia patients. Significant statistical heterogeneity was found across the 8 studies (I²=76.4%, P=0.001). The pooled mortality was 0.03(95%CI: 0.01-0.04) under random effect model, Figure 4.

Pooled mechanical ventilation ratio

The mechanical ventilation data, including invasive and non-invasive ventilation, can be extracted in 6 original studies. Significant statistical heterogeneity was also found in both invasive (I²=74.5%, P=0.001) and non-invasive (I²=83.0%, P=0.000) ventilation. The pooled invasive and non-invasive ventilation ratio were 0.03(95%CI:0.01-0.05) and 0.06(95%CI:0.02-0.09) respectively for patients with COVID-19 pneumonia, Figure 5.

Pooled clinical symptom

The top clinical symptoms of COVID-19 pneumonia were fever, cough, headache and fatigue. The pooled clinical symptom rate of fever, cough, headache and fatigue were 0.80(95%CI:0.60-1.01), 0.12(95%CI:0.08-0.17), 0.68(95%CI:0.57-0.73) and 0.51(95%CI:0.36-0.67) respectively under random effect model, Figure 6.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since Dec 2019[15], known as COVID-2019 or 2019-nCoV, has led to a major concern of the potential for not only an epidemic but a pandemic in Chia and now it seems to be a public health problem all over the world[4, 16]. Sequencing showed that COVID-19 was a new kind of β-coronavirus, which was similar to SARS-CoV[17]. Since then, COVID-19 has spread rapidly in China, especially in Wuhan[18, 19]. At the same time, COVID-19 is also spread all over the world, such as Korea[20, 21], Italy[22, 23], Japan[24, 25], the United States[26] and Iran, etc. As a new infectious disease, the clinical features and prognosis of COVID-19 is not completely clear yet[27-29]. The clinical characteristics, the proportion of severe patients and the mortality of patients with COVID-19 are different according to different individual publications. The main reason for the differences in different studies is that the sample size of each study is small with limited statistical power[30].

Therefore, we performed this meta-analysis by pooling open published data relevant to clinical characteristics of COVID-19. In the present meta-analysis, we included 10 high quality clinical studies which were published recently in the NEJM, Lancet, JAMA and et c. The original studies were all from China especially in Wuhan. The pooled data indicated that combined mortality was 0.03(95%CI: 0.01-0.04) for COVID-19 cases with random effect model. The pooled female ratio of the COVID-19 cases from 10 published data was 0.41(95%CI:0.37-0.46), which indicated male subjects seemed to be susceptible to SARS-COV-2 compared that of female. The pooled invasive and non-invasive ventilation ratio were 0.03(95%CI:0.01-0.05) and 0.06(95%CI:0.02-0.09) respectively. The combined clinical symptom of fever, cough, headache and fatigue were 0.80(95%CI:0.60-1.01), 0.12(95%CI:0.08-0.17), 0.68(95%CI:0.57-0.73) and 0.51(95%CI:0.36-0.67) respectively under random effect model, which indicating fever, cough and fatigue were the most common symptom of COVID-19 cases.

Therefore, the infection rate of male patients with SARS-COV-2 was higher than that of female patients. Less than 10% patients need invasive or non-invasive mechanical ventilation, and the overall mortality rate relative low. Most of the mortality patients were serious patients who were admitted to ICU[31]. The mortality of patients with mild disease may be even lower. However, there are some limitations in this meta-analysis. First, there is significant statistical heterogeneity across the original study. Each study uses the random effect model to combine data, resulting in increased confidence interval. Second, all patients are from the mainland of China, and most of them are in Wuhan, which may lead to patient selectivity bias. Therefore, whether the conclusion are applicable for patients from other countries remains unclear.

Consent for publication, All authors agree to published our manuscript in you journal when it accept

Availability of supporting data, Can be obtained from the corresponding author

Competing interests, No competing interest to report

Funding, no funding

Authors' contributions

Study Design, Yueming Wu

Data Collection, Shangxia Jiang, Hu Chen

Statistical Analysis, Tianzheng Lou, Hewei Xu

Data Interpretation, Yueming Wu

Manuscript Preparation, Junlong Xu

Literature Search, Yu Zhang

Acknowledgements: None

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Table 1. General characteristics of the included 10 studies

First author	Year	Region	No. included	No. death	Journal
Guan WJ[8]	2020	31 province, China	1099	15	N Engl J Med
Xu XW[6]	2020	Zhejiang, China	62	1	BMJ
Wang DW[9]	2020	Wuhan, China	138	6	JAMA
Huang CL[10]	2020	Wuhan, China	41	6	Lancet
Li Q[11]	2020	Wuhan, China	425	NA	N Engl J Med
Yang W[5]	2020	Wenzhou, China	149	0	The Journal of infection
Wu Z[7]	2020	China main land	44672	1023	JAMA
Chen N[12]	2020	Wuhan, China	99	11	Lancet
Chang D[13]	2020	Beijing, China	13	0	JAMA
Zhuang YJ[14]	2020	Beijing, China	26	NA	Chinese Journal of Nosocomiology

A meta-analysis of clinical characteristics and mortality COVID-19 pneumonia

Status:

Version 2

Abstract

Figures

Introduction

Materials and Methods

Results

Discussion

Conclusion

Declarations

References

Tables

Status:

Version 2