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. 2020 Jun 5;30(4):e2112. doi: 10.1002/rmv.2112

Comparison of confirmed COVID‐19 with SARS and MERS cases ‐ Clinical characteristics, laboratory findings, radiographic signs and outcomes: A systematic review and meta‐analysis

Ali Pormohammad 1, Saied Ghorbani 2,, Alireza Khatami 2, Rana Farzi 3, Behzad Baradaran 4,5, Diana L Turner 6, Raymond J Turner 7,, Nathan C Bahr 8, Juan‐Pablo Idrovo 9,
PMCID: PMC7300470  PMID: 32502331

Summary

Introduction

Within this large‐scale study, we compared clinical symptoms, laboratory findings, radiographic signs, and outcomes of COVID‐19, SARS, and MERS to find unique features.

Method

We searched all relevant literature published up to February 28, 2020. Depending on the heterogeneity test, we used either random or fixed‐effect models to analyze the appropriateness of the pooled results. Study has been registered in the PROSPERO database (ID 176106).

Result

Overall 114 articles included in this study; 52 251 COVID‐19 confirmed patients (20 studies), 10 037 SARS (51 studies), and 8139 MERS patients (43 studies) were included. The most common symptom was fever; COVID‐19 (85.6%, P < .001), SARS (96%, P < .001), and MERS (74%, P < .001), respectively. Analysis showed that 84% of Covid‐19 patients, 86% of SARS patients, and 74.7% of MERS patients had an abnormal chest X‐ray. The mortality rate in COVID‐19 (5.6%, P < .001) was lower than SARS (13%, P < .001) and MERS (35%, P < .001) between all confirmed patients.

Conclusions

At the time of submission, the mortality rate in COVID‐19 confirmed cases is lower than in SARS‐ and MERS‐infected patients. Clinical outcomes and findings would be biased by reporting only confirmed cases, and this should be considered when interpreting the data.

Keywords: coronavirus, COVID‐19, meta‐analysis, Middle East respiratory syndrome coronavirus, SARS virus, severe acute respiratory syndrome

1. INTRODUCTION

During the last two decades, coronaviruses have been recognized as one of the most critical human pathogenic viruses that affect global health and cause concern in the world health system. 1 Coronavirus is classified into four genera: alpha, beta, delta, and gamma. Major human pathogenic viruses belong to the beta genus, including Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and the 2019 novel coronavirus (COVID‐19). 2

Although coronaviruses are recognized as causes of the common cold, SARS was the first coronavirus to cause a life‐threatening respiratory infection in humans. It was endemic in Guangzhou China in 2002‐2003 and quickly spread to other countries in Asia, the Americas, Europe, and South Africa. A total of 8098 SARS infected cases and 774 deaths (about 10% mortality) were reported. 3

About a decade later, MERS caused respiratory infection in the Middle East. Most of these patients had a history of travel to the Arabian Peninsula, or they were in contact with infected people, of which some were camel shepherds. After the Middle East, the second outbreak of MERS occurred in 2014‐2017 in South Korea, indicating the circulation of the virus and a more significant concern for the world health community. At that time, MERS was responsible for infecting 2458 people and 848 deaths (about 35% mortality). 4

In December 2019, a cluster of Covid‐19 patients with symptoms of pneumonia complicated with acute respiratory distress syndrome (ARDS) was observed in Wuhan, China. 5 , 6 In comparison to SARS and MERS, Covid‐19 has a higher rate of spread and became a pandemic in about 4 months. The high power of this large‐scale dissemination led to the quarantine of several cities in different countries. 7 Based on the World Health Organization (WHO) 57th report on 17 March 2020; worldwide there have been 179 112 confirmed cases, with 7426 deaths (about 4% mortality). 8 There is no vaccine or targeted treatment currently available for COVID‐19 infection. Treatment is mostly supportive, although multiple experimental antiviral medications are being evaluated. 9 , 10 Thus, prevention and rapid diagnosis of infected patients are crucial. The trigger for rapid screening and treatment of COVID‐19 patients is based on clinical symptoms, laboratory, and radiographic findings that are similar to SARS and MERS infections.

In this study, we attempted to distinguish the clinical symptoms, laboratory findings, radiographic signs, and outcomes of confirmed COVID‐19, SARS, and MERS patients. All findings are compared to determine unique features among each of them. These data could be helpful in the early diagnosis and prevention of infection as well as providing more reliable epidemiological data on a large‐scale for health care policies and future studies.

2. METHODS

2.1. Search strategy

This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses Statement (PRISMA) guidelines, and it has been registered in the PROSPERO database (ID 176106). 11 We searched all studies published up to 28 February 2020, from the following databases: Embase, Scopus, PubMed, Web of Science, and the Cochrane library. Search medical subject headings (MeSH) terms used were: “COVID‐19,” “Coronavirus,” “Severe Acute Respiratory Syndrome,” “SARS Virus,” “severe acute respiratory syndrome coronavirus 2”, “Coronavirus Infections,” “Middle East Respiratory Syndrome Coronavirus,” and all their synonyms like “Wuhan Coronavirus,” “SARS‐CoV‐2,” and “COVID‐19,” “2019‐nCoV” and MERS. Moreover, we searched for unpublished and grey literature with Google scholar, Centre for Disease Controls (CDC) and WHO databases. We also examined references of included articles to find additional relevant studies. There was no language restriction, and all included studies were written in English or Chinese languages; the latter was translated by https://translate.google.com/. Additional search strategy details are provided in Table S1.

2.2. Study selection

Duplicate studies were removed using EndNote X7 (Thomson Reuters, New York, NY, USA). Records were initially screened by title and abstract by independently four authors (AP, SG, AK, and RF). The full‐text of potentially eligible records was retrieved and examined, and any discrepancies were resolved by consensus.

2.3. Eligibility and inclusion criteria

Studies had to fulfill the following predetermined criteria to be eligible for inclusion in our meta‐analysis. All case‐control, cross‐sectional, cohort studies, case reports, and case series peer‐reviewed studies were included if they reported the number of confirmed cases of patients with demographic data, [AND] [OR] clinical data, [AND] [OR] laboratory data, [AND] [OR] risk factor data.

2.4. Exclusion criteria

Studies were excluded if they did not report the number of confirmed cases. Letters to the editor, individual case reports, review articles, and news reports were also excluded. Duplicate information from the same patient was combined and counted as a single case when the data was reported twice.

2.5. Data extraction

All COVID‐19 included publications were published in 2020, and all patients were from China. The following items were extracted from each article: first author, center and study location in China, countries, sample collection time, patient follow‐up time, the reference standard for infection confirmation, number of confirmed cases, study type, and all demographic, clinical, laboratory data, and risk factor data. Three of our authors (SG, AK, and RF) independently extracted data, and all extracted data were checked randomly by another author (AP); differences were resolved by consensus.

2.6. Quality assessment

Quality assessments of studies were performed by two reviewers independently according to the Critical Appraisal Checklist recommended by the Joanna Briggs Institute, 12 and disagreements were resolved by consensus. The checklist is composed of nine questions that reviewers addressed for each study. The “Yes” answer to each question received one point. Thus, the final scores for each study could range from zero to nine (Table S2).

2.7. Analysis

Data cleaning and preparation were done in Microsoft Excel 2010 (Microsoft©, Redmond, WA, USA), and further analyses were carried out via Comprehensive Meta‐Analysis Software Version 2.0 (Biostat, Englewood, NJ). Determination of heterogeneity among the studies was undertaken using the chi‐squared test (Cochran's Q) to assess the appropriateness of pooling data. Depending on the heterogeneity test, we used either random or fixed‐effect models for pooled results. In the case of high heterogeneity (I2 > 50%), a random effect model (M‐H heterogeneity) was applied, while in low heterogeneity cases (I2 < 50%), a fixed‐effect model was used. 13 Percentages and means ± SDs were calculated to describe the distributions of categorical and continuous variables, respectively. P values reflect study heterogeneity with <.05 being significant. We also used the funnel plot, Begg's, and Egger's tests based on the symmetry assumption to detect publication bias (Figure S1).

3. RESULTS

3.1. Characteristics of included studies

The process of study selection is displayed in Figure 1. A total of 36 115 reports were screened for the analysis of patients with COVID‐19, 36 014 were excluded after the title, and abstract screening and the full text of 81 reports were reviewed in full text. We excluded studies that did not report sufficient data. Out of 114 included studies, 20 studies met the inclusion criteria for COVID‐19, 51 for SARS, 43 for MERS. The characteristics of the selected articles are summarized in Table 1. Of the 20 COVID‐19 studies that were included in the analysis, 19 studies were in English, and one was in Chinese. 21 All COVID‐19 studies were retrospective, published in 2020, and all patients were from China.

FIGURE 1.

FIGURE 1

Flow diagram of literature search and study selection (PRISMA flow chart)

TABLE 1.

Characterization of included studies

COVID‐19 studies (Total of 20 studies, 52 251 patients)
First author Sampling center/Country Sample collection time Published year Patient follow‐up (d) N Confirmed patients Mean age in years (IQR) N sex (male) Reference standard Study type
Nanshan Chen 14 Wuhan Jinyintan Hospital 1 Jan to 20 Jan 2020 2020 5‐24 99 55·5 (21‐82) 67 RT‐PCR Retrospective
Kaiyuan Sun 15 Multicenter 20 Jan‐Jan 29, 2020 2020 42 288 49 (2‐89) 62.3 CDC guideline Retrospective
Jie Li 16 Dazhou Central Hospital 22 January‐10 February 2020 2020 1‐21 17 45.1 (32‐65) 9 RT‐PCR Retrospective
Dawei Wang 17 Zhongnan Hospital of Wuhan 1 January‐28 January 2020 2020 6‐34 138 56 (42‐68) 75 RT‐PCR Retrospective
Chaolin Huang 18 Jin Yintan Hospital (Wuhan) 31 Dec 2019‐UN 2020 NA 41 49 (41‐58) 30 RT‐PCR Retrospective
Weijie Guan 19 Multicenter NA 2020 NA 1099 47 (35‐58) 640 RT‐PCR Retrospective
Yang Yang 20 NA NA 2020 51 d 4021 49 2211 NA Retrospective
Lei Chen (Chinese) 21 Tongji hospital in Wuhan 14‐29 January 2020 2020 15 d 29 56 (26‐79) 21 RT‐PCR Retrospective
Adam Bernheim 22 Multicenter 18 January‐2 February 2020 2020 12 d 121 45 (18‐80) 61 RT‐PCR & CT scan retrospective
Feng Pan 23 Union Hospital 12 Jan‐6 Feb 2020 2020 NA 21 40 (25‐63) 15 RT‐PCR Retrospective
Jin Zhang 24 No.7 hospital of Wuhan 16th Jan to 3rd Feb 2020 2020 NA 140 57 (25‐87) 71 RT‐PCR Retrospective
Yichun Cheng 25 Tongji hospital in Wuhan 28 January‐11 February 2020 2020 10 (7‐13) 710 63 (51‐71) 374 RT‐PCR Retrospective
Ming‐Yen 26 Hong Kong‐Shenzhen Hospital NA 2020 NA 21 56 (37‐65) 13 RT‐PCR Retrospective
Sijia Tian 27 Beijing Emergency Medical Service 20 Jan to 10 Feb 2020 2020 Feb. 10 20 262 47.5 (1‐94) 127 RT‐PCR Retrospective
Qun Li 28 NA NA 2020 NA 425 15‐89 (26‐82) 240 WHO guideline Retrospective
De Chang 29 Three hospitals in Beijing 16 January‐29 January 2020 2020 4 Feb. 2020 13 34 (34‐48) 10 NA Retrospective
Xiao‐Wei Xu 30 Zhejiang province 10 January‐26 January 2020 2020 10 d 62 41 (32‐52) 36 WHO guideline Retrospective
Fengxiang Song 31 Center for Disease Control, Shanghai 20 January‐27 January 2020 2020 NA 51 49 (16‐76) 25 CT scan & nucleic acid test Retrospective
Michael Chung 32 Multicenter 18‐27 January 2020 2020 NA 21 51 (29‐77) 13 CT scan, NA Retrospective
Zunyou Wu (CDC) 33 Multicenter through 11 February 2020 2020 15 d 44 672 30‐79 22 981 nucleic acid test result Retrospective
SARS studies (Total of 51 studies, 10 037 patients)
First author Sampling center/Country Sample collection time Published year Patient follow N confirmed patients Mean age in years (IQR) N sex (male) Reference standard Study type
Ali S. Omrani 34 Saudi Arabia 2013 2013 NA 3 UN UN RT‐PCR Case series
Owen Tak‐Yin Tsang 35 Hong Kong 26 January 2003‐31 March 2003 2003 NA 156 UN 90 RT‐PCR Retrospective
Li‐Yang Hsu 36 Singapore 2003 2003 NA 20 (19‐73) 5 RT‐PCR Retrospective
Christl A Donnelly 37 Hong Kong 2003 2003 NA 1425 UN UN RT‐PCR Prospective
Christopher 38 Canada 2003 2003 NA 144 (34‐57) NA RT‐PCR Retrospective
Monali Varia 39 Canada 2003 2003 NA 128 42 (21 m‐86 y) 51 RT‐PCR Retrospective
Robert A Fowler 40 Canada 2003 2003 NA 38 (39‐69.6) 23 RT‐PCR Retrospective
J S M Peiris 41 China 2003 2003 NA 50 (23‐74) NA RT‐PCR prospective
J S M Peiris 42 Hong Kong 2003 2003 NA 75 UN 36 RT‐PCR Prospective
J W M Chan 43 Hong Kong 2003 2003 NA 115 UN NA RT‐PCR Retrospective
Jann‐Tay Wang 44 Taiwan 2003 2003 NA 76 46.5 (24‐87) 34 RT‐PCR Retrospective
K L E Hon 45 China 2003 2003 NA 10 NA 2 RT‐PCR Retrospective
K. T. Wong 46 Hong Kong 2003 2003 NA 138 39 (20‐83) 66 RT‐PCR Retrospective
Kamaljit Singh 47 Singapore 2003 2003 NA 14 58 (21‐84) 5 CT scan and RT‐PCR Retrospective
Kenneth W. Tsang 48 China 2003 2003 NA 10 52.5 ± 11 5 RT‐PCR Retrospective
Marianna Ofner‐Agostini 49 Canada 2003 2006 NA 17 39.2 (27‐58) 4 RT‐PCR Retrospective
N S Zhong 50 China 2002 2003 NA 50 38.4 28 RT‐PCR Retrospective
Nelson Lee 51 China 2003 2004 NA 17 34 (22‐57) 6 RT‐PCR Retrospective
Nelson Lee 52 China 2003 2003 NA 138 NA NA RT‐PCR Cohort
P.L. Ho 53 China 2003 2005 NA 44 39.27 ± 11.26 22 RT‐PCR Retrospective
Ping Tim Tsui 54 China 2003 2003 NA 323 41 ± 14 (18‐83) NA RT‐PCR Retrospective
Raymond S M Wong 55 China 2003 2003 NA 157 NA 64 RT‐PCR Retrospective
Thomas W 56 Singapore 2003 2003 NA 199 NA 65 RT‐PCR Cohort
Timothy H Rainer 57 China 2003 2003 NA 97 37.0 ± 15.4 37 RT‐PCR Prospective
W.N. Wong 58 Hong Kong 2003 2003 NA 205 35.9 ± 16.2 90 RT‐PCR Cohort
Z. Zhao 59 China 2002 2003 NA 190 NA NA RT‐PCR Prospective
Susan M. Poutanen 60 Canada 2003 2005 NA 10 NA NA RT‐PCR Retrospective
I.F.N. Hung 61 China 2004 2004 NA 154 41.5 (20‐80) 92 RT‐PCR Retrospective
Hoang Thu Vu 62 Vietnam 2003 2004 NA 62 NA NA RT‐PCR Retrospective
F. Chena 63 Hong Kong 2002 2004 NA 10 NA 5 RT‐PCR Retrospective
C.W. Leung 64 China 2004 2004 NA 64 11.7 29 RT‐PCR Retrospective
Monica Avendano 65 Canada 2003 2003 NA 14 42 ± 9 (27‐63) 3 RT‐PCR Retrospective
Padmini Srikantiah 66 Us 2003 2005 NA 8 NA NA RT‐PCR Retrospective
Kwok H. Chan 67 Hong Kong 2004 2004 NA 322 NA NA RT‐PCR Cohort
Wannian Liang 68 China 2003 2003 NA 2443 33 (1.0‐90) NA RT‐PCR Prospective
Xinchun Chen 69 China 2004 2004 NA 36 30.39 ± 12.15 20 RT‐PCR Retrospective
Chi‐wai Leung 70 Hong Kong 2004 2004 NA 44 12 (17‐50) 20 RT‐PCR Prospective
LCL Heung 71 Hong Kong 2006 2006 NA 93 NA 18 IF Cross‐sectional
Ming‐Han Tsai 72 Taiwan. 2003 2008 NA 124 NA NA ELISA Retrospective
Hy A. Dwosh 73 Us 2003 2003 NA 16 (24‐80) 4 RT‐PCR Retrospective
Ari Bitnun 73 Canada 2003 2003 NA 15 NA 6 RT‐PCR Prospective
Alice S. Ho 74 Hong Kong 2003 2003 NA 40 (24‐50) 9 RT‐PCR Retrospective
Leonard Grinblat 75 Canada 2003 2003 NA 40 42.7 ± 13.5 (17‐73) 18 RT‐PCR Retrospective
Cheng‐Kuo Fan 76 Taiwan 2005 2005 NA 43 41.0 ± 17.1 22 RT‐PCR Descriptive
Kin Wing Choi 77 Hong Kong 2003 2003 NA 227 39 (18‐96) 75 RT‐PCR Retrospective
GM Leung 78 Hong Kong 2003 2003 NA 1755 NA 777 RT‐PCR Retrospective
Chung‐Ming Chu 79 China 2005 2005 NA 79 39.4 ± 11.5 (20‐72) 38 RT‐PCR Retrospective
Kwok Hong Chu 80 Hong Kong 2004 2004 NA 536 NA NA RT‐PCR Retrospective
T.‐N. Jang 81 Taiwan 2003 2004 NA 29 42.9 (22‐82) 9 RT‐PCR Retrospective
Tze‐wai Wong 82 China 2004 2004 NA 16 22.3 8 RT‐PCR Retrospective
Wei‐Kung Wang 83 Taiwan 2003 2004 NA 17 21‐54 9 RT‐PCR Retrospective
MERS studies (Total 43 studies, 8, 139 patients)
First author Sampling center/Country Sample collection time Published year Patient follow N Confirmed patients Mean age in years (IQR) N Sex (male) Reference standard Study type
Asad S. Aburizaiza 84 Saudi Arabia 2012 2012 NA 8 (16‐62) NA IFA Cross‐sectional
Marcel A Müller 85 Saudi Arabia 2012‐2013 2015 NA 15 37·13 ± 8·64 (15‐62) NA ELISA, IFA Cross‐sectional
Abdulkarim Alhetheel 86 Saudi Arabia 2016 2017 NA 30 NA NA RT‐PCR Cross‐sectional
Abdulaziz A. Bin Saeed 87 Saudi Arabia 2015 2016 NA 384 (1‐66) 226 NA Cross‐sectional
Boyeong Ryu 88 South Korea 2015 2015 NA 34 (34‐56.7) 20 RT‐PCR Cross‐sectional
Jamal Ahmadzadeh 89 Iran 2019 2019 NA 107 50 ± 17 80 NA Cross‐sectional
Kazhal Mobaraki 90 Iran 2019 2019 NA 229 NA 171 RT‐PCR Epidemiological analysis
Abdullah Assiri 91 Saudi Arabia 2013 2013 NA 47 55 36 RT‐PCR Retrospective
Korea Centers for Disease 92 South Korea 2015 2015 NA 186 55 (42‐66) 111 RT‐PCR Retrospective
Abdullah Assiri 93 Saudi Arabia 2013 2013 NA 23 56 (24‐94) 17 RT‐PCR Retrospective
Abdullah Assiri 94 Saudi Arabia 2014 2016 NA 38 51 (17‐84) 28 RT‐PCR Retrospective
Abdullah M. Assiri 95 Saudi Arabia 2015 2016 NA 143 58 (2.0‐99) 91 RT‐PCR Retrospective
Ashraf Abdel Halim 96 Egypt 2015 2016 NA 32 43.99 ± 13.03 20 RT‐PCR Retrospective
Deborah L. Hastings 97 Saudi Arabia 2014 2016 NA 78 53 59 RT‐PCR Retrospective cohort
F S Alhamlan 98 Saudi Arabia 2012‐2015 2016 NA 1275 50 (0‐109) 807/1246 RT‐PCR Retrospective
H.E. El Bushra 99 Saudi Arabia 2015 2016 NA 52 NA 31 RT‐PCR Retrospective
Hanan H. Balkhy 99 Saudi Arabia 2016 2016 NA 130 56.3 66 RT‐PCR Retrospective
Ikwo K. Oboho 100 Saudi Arabia 2014 2015 NA 255 45 (30‐59) 174 RT‐PCR Retrospective
Kyung Min Kim 101 South Korea 2015 2015 NA 36 51 20/36 RT‐PCR Retrospective
Ziad A. Memish 102 Saudi Arabia 2013 2013 NA 7 (29‐59) 0 RT‐PCR Retrospective
Won Suk Choi 103 South Korea 2015 2015 NA 186 5 (16‐86) 111 RT‐PCR Retrospective observational
Mohammad Mousa Al‐Abdallat 104 Jordon 2012 2014 NA 9 40 (25‐60) 6 RT‐PCR Retrospective
Mustafa Saad 105 Saudi Arabia 2012‐2014 2014 NA 70 62 (1‐90) 46 RT‐PCR Retrospective
Yaseen M. Arabi 106 Saudi Arabia 2012‐2013 2014 NA 12 59 (36‐83) 8 RT‐PCR Case series
Maimuna S. Majumder 107 South Korea 2015 2015 NA 159 55 ± 15.9 (16‐87) 94 RT‐PCR Retrospective
Victor Virlogeux 108 South Korea 2015 2016 NA 107 54.6 96 NA Retrospective
Jaffar A. Al‐Tawfiq 109 Saudi Arabia NA 17 60.7 11 RT‐PCR Case‐control
Thamer H. Alenazi 110 Saudi Arabia 2015 2017 NA 130 56.5 66 RT‐PCR Prospective
Abdullah J. Alsahafi 111 Saudi Arabia 2012‐2015 NA 939 NA 624 NA
Karuna M. Das 112 Saudi Arabia 2015 2015 NA 55 54 ± 16 (12 to 85) 16 RT‐PCR Retrospective
Anwar E. Ahmed 113 Saudi Arabia 2014‐2016 2017 NA 660 53.9 ± 17.9 (2‐109) 452 NA Retrospective
Anwar E. Ahmed 114 WHO website 2015‐2017 2017 NA 537 55 ± 17.9 (2‐109) 370 NA Retrospective
Basem M. Alraddadi 115 Saudi Arabia 2014 2014 NA 535 49 518 NA Retrospective
Benjamin J Cowling 116 South Korea 2015 2015 NA 166 56 101 NA Retrospective
Chang Kyung Kang 117 South Korea 2015 2017 NA 186 54 111 RT‐PCR Retrospective
Christian Drosten 118 Saudi Arabia 2014 2014 NA 12 (3‐74) 7 PRNT and RT‐PCR Cross‐sectional
Daniel R. Feikin 119 Saudi Arabia 2014 2015 NA 102 NA 76 NA retrospective
Hamzah A. Mohd 120 Saudi Arabia 2014‐2015 2016 NA 80 40 48 RT‐PCR Cohort
Jung Wan Park 121 South Korea 2015 2017 NA 26 71 (38‐86) 13 RT‐PCR Retrospective
Nahid Sherbini 122 Saudi Arabia 2014 2016 NA 29 45 ± 12 20 RT‐PCR Retrospective
Oyelola A. Adegboye 123 Saudi Arabia 2012‐2015 2017 NA 959 NA 642 NA
Ghaleb A. Almekhlafi 124 Saudi Arabia NA 31 59 ± 20 22 RT‐PCR Retrospective cohort
Sun Hee Park 125 South Korea NA 23 NA 13 RT‐PCR Retrospective

Abbreviations: CDC, Centers for Disease Control and Prevention; CT scan, CT scan of chest; IQR, interquartile range; N, number; NA, not known; RT‐PCR, real‐time polymerase chain reaction; WHO, World Health Organization.

3.2. Quality assessment

Quality assessment of included studies was performed based on the Critical Appraisal Checklist, and the final quality scores of the included studies are represented in Table S2. In brief, studies by Chen et al, 14 Wang et al, 17 Huang et al, 18 Guan et al, 19 Zhang et al, 24 Cheng et al, 25 Li et al, 28 Xu et al, 30 and Song et al 31 had the highest quality of the COVID‐19 studies available in the purpose of this study.

3.3. Demographics, baseline characteristics, and clinical characterization

Overall, 52 251 confirmed patients with COVID‐19 infection, 10 037 with SARS, and 8139 with MERS were included in the meta‐analysis, of which 53.7% (95% CI 50‐56.8, P < .001) of COVID‐19, 43% (95% CI 40‐46.5, P < .001) of SARS, 66% (95% CI 63‐69, P < .001), of MERS included patients were male. Funnel plots for included studies did not detect significant publication bias (Figure S1). Table 2 shows that most COVID‐19 85.6% (95% CI 73‐93, P < .001), SARS 96% (95% CI 93‐97.6, P < .001), and MERS 74% (95% CI 63.5‐83.5, P < .001) had a fever (Figure S2). Cough was the second most common symptom presenting in COVID‐19 63% (95% CI 55.5‐70, P < .001), SARS 54.2% (95% CI 49‐59, P < .001), and MERS 61% (95% CI 51‐70, P < .001) of patients (Figure S3).

TABLE 2.

Demographics, baseline characteristics, and clinical outcomes of patients with confirmed COVID‐19

COVID‐19 (Total of 20 Studies, 52, 251 Patients) SARS (Total of 51 Studies, 10, 037 Patients) MERS (Total 43 Studies, 8, 139 Patients)
Clinical presentation a (CI 95%) Included studies number Included patients number Clinical presentation a (CI 95%) Included studies number Included patients number Clinical presentation a (CI 95%) Included studies number Included patients number
Age, y

49.5 (mean)

(46‐52.5)

20 52 251

37.5

(34.5‐40.5)

24 4309

52

(51‐54.5)

30 5174
Sex (Male)

53.7

(50‐56.8)

20 52 248

43 (%)

(40‐46.5)

35 6254

66

(63‐69)

40 8086
Fever

85.6

(73‐93)

15 2832

96

(93‐97.6)

34 6194

74

(63.5‐83.5)

22 1583
Cough

63

(55.5‐70)

15 2135

54.2

(49‐59)

32 5904

61

(51‐70)

21 1453
Fatigue

40.3

(29‐52.5)

11 1959

28

(21‐35)

6 516
Sputum production/Expectoration

28

(19‐39)

7 1378

21

(16‐27)

11 2320

31.5

(22‐43)

9 757
Myalgia

26

(14‐43)

6 1350

49.5

(44.5‐55)

22 2872

33.3

(26.5‐41)

10 785
Dyspnea

20

(12.6‐32)

7 1730

32

(20.5‐45.5)

18 2412

40

(23‐57)

11 777
Shortness of breath

17

(9‐31.5)

3 1260

32

(20‐46)

11 2335

51

(41‐63)

9 695
Chill

17

(6.5‐38)

2 1120

57.5

(50‐64)

21 2767

41

(16‐72)

6 667
Sore throat

12.3

(7.8‐17)

6 1429

17

(14‐21)

20 2452

16.5

(10‐26)

12 992
Headache

12.2

(8.3‐18)

10 1815

38

(30‐46)

20 2617

15

(11‐20)

12 1170
Diarrhea

7.3

(4.6‐11.4)

11 1710

24

(17.5‐31.5)

20 2452 17.3 (14.5‐20.5) 13 1017
Rhinorrhea

6

(3‐12)

3 129

13

(8.5‐20)

6 840 6 (1‐20) 6 479
Nausea and vomiting

6

(2.7‐13)

4 1387

18.5

(13‐25

14 2410

20

(16‐25)

12 863
Runny nose

4

(1‐14)

1 51

18

(9‐30)

6 870

21

(4‐61)

5 246
Comorbid conditions
COVID‐19 SARS MERS
Clinical presentation a (CI 95%) Included studies number Included patients number Clinical presentation a (CI 95%) Included studies number Included patients number Clinical Presentation a (CI 95%) Included studies number Included patients number
Recent travel or contact with endemic people resident of Wuhan

69.5

(54.5‐81)

7 45 443

26.5

(20‐34)

1 156
Chronic diseases

41.2

(20‐66)

3 1227
Exposure to seafood market

24.3

(9.6‐49)

5 732
Sick contacts with respiratory illness

15

(4.5‐39.6)

4 829
Hypertension

15

(8.5‐24.6)

10 46 270

14

(5.5‐31)

4 504

36

(28‐45)

10 677
ARDS

10.6

(4‐26.7)

5 1439

51

(6‐94)

2 204

29

(14‐51)

2 55
Diabetes

8

(4‐15)

8 46 232

9.9

(5‐16.5)

10 2304

46

(34.5‐58)

17 1086
Current smoker

7.7

(3.7‐15)

5 1348

7.5

(5‐11)

4 347

21.5

(14‐32)

9 144
Chronic liver disease

5.7

(3.8‐8.4)

8 499

13.5

(5‐30)

6 604

9

(4‐21)

5 53
Digestive system disease

3.5

(2.5‐4.9)

2 1198

10.5

(6.5‐6)

5 504

16.5

(10‐25)

11 152
Health care worker

3

(2‐4.6)

3 46 196

28.5

(18‐43)

12 2328

21

(17‐25.5)

20 1232
Past smoker

3

(1.1‐7.5)

2 1239
Cardiovascular and cerebrovascular diseases

2.3

(2.2‐2.5)

8 46 302

9.5

(5‐22)

8 1045

20.5

(15‐27)

15 407
Chronic respiratory disease

2.2

(0.6‐8)

4 45 911

30

(15‐50)

10 2224

9

(6.5‐12

1 939
Cancer

1.7

(0.4‐7.4)

6 46 078

1.3

(0.2‐10)

3 504

12

(7‐20)

10 182
Renal failure

2.3

(1‐4)

7 2289

4

(2.5‐7)

8 1103

20.5

(14‐24.5)

15 366

Bacteria

co‐infection

20

(12‐31)

3 281

17.7

(6‐42)

4 21
Camel exposure

20

(12‐32)

9 657
Chest X‐ray and CT scan
COVID‐19 SARS MERS
Clinical presentation a (CI 95%) Included studies number Included patients number Clinical presentation a (CI 95%) Included studies number Included Patients Number Clinical presentation a (CI 95%) Included studies number Included patients number
Abnormal chest X ray

84

(78‐8.5)

12 1706

86

(77‐92)

20 1209

74.7

(56.5‐87)

10 258
Bilateral involvement

76.8

(62.5‐87)

12 46 270
Consolidation

75.5

(50.5‐91)

6 1378

41.5

(11‐80)

2 78

18

(10‐30)

1 10
Ground‐glass opacity

71

(40‐90)

12 46 270

41

(14‐76

3 340

65

(52‐77)

1 36
Unilateral involvement of chest radiography

16.5

(8.5‐29.5)

6 1378
Outcome
COVID‐19 SARS MERS
Clinical presentation a (CI 95%) Included studies number Included patients number Clinical presentation a (CI 95%) Included studies number Included patients number Clinical presentation a (CI 95%) Included studies number Included patients number
Hospitalized

85.4 (%)

(68‐94)

3 1378

33

(11‐66)

3 87

8

(1‐40)

5 1400
Discharged

14 (%)

(5.55‐31.5)

3 1378

40

(28‐53)

7 1660
Critical condition/ICU

20.6 (%)

(6.7‐48)

6 45 951
Mortality

5.6 (%)

(2.5‐12.5)

8 47 200

13

(9‐17)

20 5501

35

(31‐39)

32 6987

Abbreviations: ARDS, acute respiratory distress syndrome; CI, confidence interval; CT scan, CT scan; ICU, intensive care unit.

a

Age is an exception, presented in mean age in years.

Shortness of breath was less common in Covid‐19 patients 17% (95% CI 9‐31.5, P < .001), in comparison to SARS 32% (95% CI 20‐46, P < .001), and MERS 51% (95% CI 41‐63, P < .001). Likewise, chills were less common in Covid‐19 patients 17% (95% CI 6.5‐38, P < .001), in comparison to SARS 57.5% (95% CI 50‐64, P < .001), and MERS 41% (95% CI 16‐72, P < .001).

A much smaller proportion of COVID‐19 patients had sore throat 12.3% (95% CI 7.8‐17, P < .06), headache 12.2% (95% CI 8.3‐18, P < .001), diarrhea 7.3% (95% CI 4.6‐11.4, P < .001), rhinorrhea 6% (95% CI 3‐12, P < .43), nausea and vomiting 6% (95% CI 2.7‐13, P < .001), or runny nose 6% (95% CI 1‐14, P < .001). More detail information about demographics and clinical characterization of COVID‐19 (Table S3), SARS (Table S4), and MERS patients (Table S5) demonstrated in the supplementary material.

3.4. Risk factors and clinical characteristics of patients infected with COVID‐19

The greatest risk for COVID‐19 patients 69.5% (95% CI 54.5‐81, P < .001) up to 28 February 2020, is a history of recent travel to Wuhan, contact with people from Wuhan, or were Wuhan residents, and 24.3% (95% CI 9.6‐49, P < .001) had exposure at the seafood market(s). The most common comorbid chronic condition for COVID‐19 and SARS is hypertension, and for MERS diabetes, 46% (95% CI 34.5‐58, P < .001). Overall, 41.2% (95% CI 20‐66, P < .001) of COVID‐19 patients had a history of chronic diseases. Acute respiratory syndrome (ARDS) occurred more frequently in SARS 51% (95% CI 6‐94, P < .001) compared to MERS 29% (95% CI 14‐51, P < .001) and COVID‐19 10.6% (95% CI 4‐26.7, P < .001). More detailed information about comorbid conditions of COVID‐19 (Table S6), SARS (Table S7), and MERS (Table S8) patients is demonstrated in the supplementary material.

3.5. Chest X‐ray and CT scan findings in patients infected with COVID‐19

Analysis showed that 84% (95% CI 78‐8.5, P < .001) of COVID‐19 patients, 86% (95% 77‐92, P < .001) of SARS patients, and 74.7% (95% 56.5‐87, P < .001) of MERS patients had abnormal radiological findings on chest X‐ray and CT scans. The radiological abnormalities in COVID‐19 patients were bilateral involvement of chest X‐ray 76.8% (95% CI 62.5‐87, P < .001), consolidation 75.5% (95% CI 50.5‐91, P < .001), and ground‐glass opacity 71% (95% CI 40‐90, P < .001) (Table 2). More detailed information about chest X‐ray and CT scan findings of COVID‐19 (Table S9), SARS (Table S10), and MERS patients (Table S11) is demonstrated in the supplementary material.

3.6. Outcome

Most COVID‐19 confirmed patients required hospitalization 85.4% (95% CI 68‐94, P < .001) and 20.6% (95% CI 6.7‐48, P < .001) were deemed to be in critical condition. The mortality rate of COVID‐19 confirmed cases was 5.6% (95% CI 2.5‐12.5, P < .001), SARS 13% (95% 9‐17, P < .001), and MERS 35% (95% CI 31‐39, P < .001) (Figure 2 ).

FIGURE 2.

FIGURE 2

Forest plot of the meta‐analysis on mortality outcome in patients with confirmed COVID‐19 (upper left), SARS (upper right), and MERS (lower left)

3.7. Laboratory findings of patients infected with COVID‐19

The laboratory findings showed that among a subset of patients 4.5% (2361/52 251) where data were available, thrombocytosis in COVID‐19 patients was 61% (95% CI 45‐72, P < .001) which is more than double that of SARS at 41.5% (95% CI 35‐56.4, P < .001) and MERS 30% (95% CI 22‐58, P < .001) (Table 3). The most SARS patients 71% (95% CI 62‐78, P < .001) had decreased lymphocytes, and the most of MERS patients had decrease platelets 62% (95% 52‐74, P < .001) in their laboratory findings (Table 3 ).

TABLE 3.

Laboratory features for confirmed patients with COVID‐19

Normal range Mean (CI 95%) Total patient number Number of studies Mean (CI 95%) Total patient number Number of studies Mean (CI 95%) Total patient number Number of studies
COVID‐19 SARS MERS
Leucocytes (WBCs) 3.5‐9.5

5.55 (×109 per L)

(5.1‐5.9)

2361 11

5.1 (×109 per L)

(3.3‐7)

367 8

7.4 (×109 per L)

(6‐8.7)

280 5
Increased 13.3 (%) 28 (%) 30 (%)
Decreased 26 (%) 32 (%) 41 (%)
Neutrophils 1.8‐6.3

3.6 (×109 per L)

(3.1‐4.1)

412 8

4.6

(4.6‐7.1)

614 5

5.3

(5‐5.5)

150 2
Increased 5 (%)
Decreased 17.5 (%)
Lymphocytes 1.1‐3.2

0.98 (×109 per L)

(0.9‐1.06)

2361 11

0.74 (×109 per L)

(0.66‐0.816)

825 10 210 4
Decreased 62.5 (%) 71 (%) 50 (%)
Platelets 125‐350

186.5 (×109 per L)

(167‐205)

2200 9

179 (×109 per L)

(159‐199)

1912 5 178 3
Decreased 13 (%) 0.2 (%) 62 (%)
Increased 61 (%) 41.5 (%) 30 (%)
CRP a 0‐0.5

29.6 (mg/L)

(16.7‐42.5)

290 5

22.8 (mg/L)

(22‐35)

256 2 156 3
Increased 81 (%) 93 (%) 45 (%)
Hemoglobin 130‐175

119 (g/L)

(106‐132)

2062 8
ESR b 0‐15

42 (mm/h)

(46‐57)

120 2

Albumi

Decreased

40‐55

36.8 (g/L)

(24.5‐46)

80%

120 2

Interleukin‐6

Increased

0.0‐7

7.9 (mg/mL)

(6.8‐8.6)

52%

99 2
LDH c 120‐250

280

(268‐294)

1783 9
Increased 70.3 (%)

Abbreviations: CRP, C reaction protein; ESR, erythrocyte sedimentation rate; WBCs, white blood cells.

a

Increased or decreased refers to values above or below the normal range.

b

erythrocyte sedimentation rate.

c

Lactate dehydrogenase.

4. DISCUSSION

Prior to 2002, coronaviruses were associated with mild respiratory illness, but with the emergence of SARS in 2002, MERS in 2012, and now in late 2019, COVID‐19, it is established that coronaviruses infections can be associated with severe respiratory disease. The virus is transmitted via respiratory droplets or infected inanimate objects, and with its rapid spread worldwide in just a few months, the WHO has officially declared the COVID 19 outbreak a pandemic. 22 , 126

Our results show that fever and cough were the most common clinical symptoms in COVID‐19, SARS, and MERS. Among 52 251 patients with COVID‐19 infection, while fatigue, sputum production, and myalgia (muscle soreness) were the next most frequent clinical symptoms; diarrhea, rhinorrhea, nausea, and vomiting were less common. Within the 10 037 confirmed SARS patients, the next most frequent clinical manifestations were chills, myalgia, headache, and dyspnea. Moreover, 8139 MERS patients commonly exhibited shortness of breath, chills, and dyspnea.

Shortness of breath was less common in COVID‐19 patients (17%), in comparison to SARS (32%) and MERS (51%). Likewise, chills were less common in COVID‐19 patients (17%), in comparison to SARS (57.5%) and MERS (41%). Therefore, these clinical symptoms should help distinguish the various coronavirus infections from each other.

Our analysis indicated recent travel to Wuhan, contact with people from Wuhan or residency in Wuhan, exposure to persons with respiratory symptoms, and seafood market exposures were common risks among those contracting COVID‐19. Furthermore, chronic respiratory disease and recent travel to SARS endemic areas were most common among those contracting SARS. In addition, 28% of SARS patients and 21% of MERS confirmed patients were health care workers, which is higher than COVID‐19 cases (3%). This data indicate that in coronavirus outbreaks, isolating infected individuals is one of the most important ways of controlling transmission.

We find that most of the patients with COVID‐19, SARS, and MERS had abnormal chest radiological findings. With ground‐glass opacity and consolidation in COVID‐19 patients being more frequent than in SARS and MERS patients. Other studies reported that significant similarity exists when comparing radiological findings of COVID‐19 patients with those suffering from complicated viral pneumonia such as SARS and MERS. 22 , 32 Therefore, there appear to be no distinguishing radiological findings when comparing human coronaviruses.

The mortality rate was 5.6%, 13%, and 35% among COVID‐19‐, SARS‐, and MERS‐infected patients, respectively. While the mortality rate among COVID‐19 patients is lower than SARS and MERS, COVID‐19 is proving to have a higher contagious potency, resulting in a higher number of deaths. It should be recognized that these numbers are biased due to the data set, including publications related to screening practices (eg, only those with symptoms being screened) increased the percentage value. The actual mortality rate from COVID‐19 is almost certainly much lower than that found in this study. As more data emerges from screening asymptomatic or mildly symptomatic individuals in China and around the world, the exact mortality rate will be better understood.

Among COVID‐19, SARS, and MERS patients, leukocytosis was found in 13.3%, 28%, and 30%, respectively, and leukopenia in 26%, 32%, and 41%, respectively.

Most of the patients with coronavirus had abnormal chest radiological findings. On the other hand, runny nose and rhinorrhea are less common symptoms in coronavirus‐infected patients, 127 which indicates the virus preferentially affects the lower respiratory tract. A study by Zhao et al showed that ACE2 is a COVID‐19 virus receptor and that it is typically expressed on pulmonary alveolar epithelial cells. 128 Another study reported that following COVID‐19 infection deregulated cytokine/chemokine response and higher virus titer causes an inflammatory cytokine storm with lung immunopathological injury. 129 Inflammation related to the cytokine storm in the lungs may then spread throughout the body via the circulation system. COVID‐19 patients have been reported to have increased plasma concentration of inflammation‐related cytokines, including interleukin (IL)‐2,6,7,10, tumor necrosis factor‐α (TNF‐α), and monocyte chemoattractant protein I (MCP‐I) especially in moribund patients. 130 Our data collected here show that ARDS occurred in 10.6% of reported patients with COVID‐19 infection. A previous study showed that ACE2 (main receptor of COVID‐19) expression is higher in people with pulmonary ARDS and acute respiratory injury. 131

Several limitations of this study exist. Publication bias and study heterogeneity are unavoidable in this type of study. Therefore, it should be considered when interpreting the outcomes of the reports and our final data set. Furthermore, this study likely overestimates disease severity due to a lack of screening for asymptomatic or mildly symptomatic individuals and subsequent publication bias related to these factors. Likely, many infected persons have not been detected, thus falsely elevating the rates of hospitalization, critical condition, and mortality. The lower quality analysis and reporting in some of the included publications is another limitation of the study. To prevent language bias, we included reports in languages other than English. Additionally, we searched for a variety of sites and databases to prevent internet platform bias. Using Egger's regression test, we did not find significant publication bias. Journal bias is an issue facing those who carry out a meta‐analysis, yet it does not usually affect the general conclusions. 132 However, we cannot reject the occurrence of other biases in this study, such as choice bias, since several journals are not indexed in Embase, Scopus, PubMed, Web of Science, and the Cochrane library and unpublished data from some regions of the world.

5. CONCLUSIONS

Fever and cough are the most common symptoms of COVID‐19‐, SARS‐, and MERS‐infected patients. The mortality rate in COVID‐19 confirmed cases was lower than SARS‐ and MERS‐infected patients. Clinical outcomes and findings may be biased by reporting only confirmed cases, and it should be considered when interpreting the data.

CONFLICT OF INTEREST

The authors have declared that no conflict of interests.

AUTHOR CONTRIBUTIONS

Conceived and designed the study: A.P., S.G.

Comprehensive research: S.G., A.K., A.P., R.F.

Analyzed the data: A.P.

Wrote and revised the paper: A.P., S.G., A.K., R.F., B.B., D.T., R.T., N.B., J.P.I.

Participated in data analysis and manuscript editing: A.P., S.G., A.K., R.F., B.B., D.T., R.T., N.B., J.P.I.

ETHICAL STATEMENT

The manuscript is a systematic review, so the ethical approval was not required for the study.

Supporting information

Figure S1. Funnel‐plot for the Standard Error by Logit Event rate to assess for publication bias of included studies for COVID‐19, SARS, and MERS.

Figure S2. Forest plot of the meta‐analysis on clinical presentation of fever in patients with Confirmed COVID‐19, SARS, and MERS.

Figure S3. Forest plot of the meta‐analysis on clinical presentation of cough in patients with Confirmed COVID‐19, SARS, and MERS.

Table S1. Search strategy.

Table S2. Quality assessment of included studies.

Table S3. Demographics, Baseline Characteristics, and Clinical Presentations and Outcomes of Patients with Confirmed COVID‐19.

Table S4. Demographics, Baseline Characteristics, and Clinical Presentations and Outcomes of Patients with Confirmed SARS.

Table S5. Demographics, Baseline Characteristics, and Clinical Presentations and Outcomes of Patients with Confirmed MERS.

Table S6. Clinical Characteristics and Comorbid Conditions of patients with confirmed COVID‐19.

Table S7. Clinical Characteristics and Comorbid Conditions of patients with confirmed SARS.

Table S8. Clinical Characteristics and Comorbid Conditions of patients with confirmed MERS.

Table S9. Chest X‐ray and CT scan Findings in Patients with Confirmed COVID‐19.

Table S10. Chest X‐ray and CT scan Findings in Patients with Confirmed SARS.

Table S11. Chest X‐ray and CT scan Findings in Patients with Confirmed MERS.

ACKNOWLEDGEMENTS

None.

Pormohammad A, Ghorbani S, Khatami A, et al. Comparison of confirmed COVID‐19 with SARS and MERS cases ‐ Clinical characteristics, laboratory findings, radiographic signs and outcomes: A systematic review and meta‐analysis. Rev Med Virol. 2020;30:e2112. 10.1002/rmv.2112

Abbreviations: ACE2, angiotensin‐converting enzyme 2; ARDS, acute respiratory distress syndrome; CDC, Centre for Disease Controls; CI, confidence interval; COVID‐19, coronavirus disease 2019; CRP, C‐reaction protein; CT scan, computed tomography scan; ESR, erythrocyte sedimentation rate; GGO, ground‐glass opacity; ICU, intensive care unit; IL, interleukin; IQR, interquartile range; MCP‐I, monocyte chemoattractant protein I; MERS, Middle East respiratory syndrome; N, number; NA, not known; PRISMA, preferred reporting items for systematic reviews and meta‐analyses statement; RT‐PCR, real‐time polymerase chain reaction; SARS, severe acute respiratory syndrome; SARS‐Cov‐2, severe acute respiratory syndrome coronavirus‐2; TNF‐α, tumor necrosis factor‐α; WBCs, white blood cells; WHO, World Health Organization.

Contributor Information

Saied Ghorbani, Email: vet.s.ghorbani@gmail.com.

Raymond J. Turner, Email: turnerr@ucalgary.ca.

Juan‐Pablo Idrovo, Email: juan.idrovo@cuanschutz.edu.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Figure S1. Funnel‐plot for the Standard Error by Logit Event rate to assess for publication bias of included studies for COVID‐19, SARS, and MERS.

Figure S2. Forest plot of the meta‐analysis on clinical presentation of fever in patients with Confirmed COVID‐19, SARS, and MERS.

Figure S3. Forest plot of the meta‐analysis on clinical presentation of cough in patients with Confirmed COVID‐19, SARS, and MERS.

Table S1. Search strategy.

Table S2. Quality assessment of included studies.

Table S3. Demographics, Baseline Characteristics, and Clinical Presentations and Outcomes of Patients with Confirmed COVID‐19.

Table S4. Demographics, Baseline Characteristics, and Clinical Presentations and Outcomes of Patients with Confirmed SARS.

Table S5. Demographics, Baseline Characteristics, and Clinical Presentations and Outcomes of Patients with Confirmed MERS.

Table S6. Clinical Characteristics and Comorbid Conditions of patients with confirmed COVID‐19.

Table S7. Clinical Characteristics and Comorbid Conditions of patients with confirmed SARS.

Table S8. Clinical Characteristics and Comorbid Conditions of patients with confirmed MERS.

Table S9. Chest X‐ray and CT scan Findings in Patients with Confirmed COVID‐19.

Table S10. Chest X‐ray and CT scan Findings in Patients with Confirmed SARS.

Table S11. Chest X‐ray and CT scan Findings in Patients with Confirmed MERS.


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