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.

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.
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.

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.
Increased or decreased refers to values above or below the normal range.
erythrocyte sedimentation rate.
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.
REFERENCES
- 1. Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. Lancet. 2020;395(10223):470‐473. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Guarner J. Three Emerging Coronaviruses in Two Decades: the Story of SARS, MERS, and Now COVID‐19. Oxford: Oxford University Press; 2020. [Google Scholar]
- 3. Hui D, Chan M, Wu A, Ng P. Severe acute respiratory syndrome (SARS): epidemiology and clinical features. Postgrad Med J. 2004;80(945):373‐381. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Hui DS, Azhar EI, Kim Y‐J, Memish ZA, Oh M‐D, Zumla A. Middle East respiratory syndrome coronavirus: risk factors and determinants of primary, household, and nosocomial transmission. Lancet Infect Dis. 2018;18(8):e217‐e227. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Chan JF‐W, Yuan S, Kok K‐H, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person‐to‐person transmission: a study of a family cluster. Lancet. 2020;395(10223):514‐523. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. Gates B. Responding to Covid‐19—A once‐in‐a‐century pandemic? N Engl J Med. 2020;382(18):1677‐1679. [DOI] [PubMed] [Google Scholar]
- 8. WHO . Rational use of personal protective equipment for coronavirus disease 2019 (COVID‐19). 2020. https://apps.who.int/iris/bitstream/handle/10665/331215/WHO-2019-nCov-IPCPPE_use-2020.1-eng.pdf. Accessed February 27, 2020.
- 9. Contini A. Virtual Screening of an FDA Approved Drugs Database on Two COVID‐19 Coronavirus Proteins. 2020. MedRxiv. [Google Scholar]
- 10. Zhavoronkov A, Aladinskiy V, Zhebrak A, et al. Potential COVID‐2019 3C‐like Protease Inhibitors Designed Using Generative Deep Learning Approaches. 2020;307:E1. Hong Kong: Insilico Medicine Ltd. [Google Scholar]
- 11. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta‐analyses: the PRISMA statement. Ann Intern Med. 2009;151(4):264‐269. [DOI] [PubMed] [Google Scholar]
- 12. Munn Z, Moola S, Riitano D, Lisy K. The development of a critical appraisal tool for use in systematic reviews: addressing questions of prevalence. Int J Health Policy Manage. 2014;3:123‐128. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies. J Natl Cancer Inst. 1959;22(4):719‐748. [PubMed] [Google Scholar]
- 14. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507‐513. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. Sun K, Chen J, Viboud C. Early epidemiological analysis of the 2019‐nCoV outbreak based on a crowdsourced data. medRxiv. 2020. [DOI] [PMC free article] [PubMed]
- 16. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;471:657‐665. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–Infected pneumonia in Wuhan, China, China. JAMA 2020;244(2014):2464‐2475. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497‐506. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19. W‐j Guan, Z‐y Ni, Hu Y, et al. Clinical characteristics of 2019 novel coronavirus infection in China. MedRxiv. 2020.
- 20. Yang Y, Lu Q, Liu M, et al. Epidemiological and clinical features of the 2019 novel coronavirus outbreak in China. medRxiv. 2020.
- 21. Chen L, Liu H, Liu W, et al. Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia. Chin J Tuberc Respir Dis [Zhonghua jiehe he huxi zazhi]. 2020;43:E005. [DOI] [PubMed] [Google Scholar]
- 22. Bernheim A, Mei X, Huang M, et al. Chest CT findings in coronavirus Disease‐19 (COVID‐19): relationship to duration of infection. Radiology. 2020;200463:142‐150. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23. Pan F, Ye T, Sun P, et al. Time course of lung changes on chest CT during recovery from 2019 novel coronavirus (COVID‐19) pneumonia. Radiology. 2020;3(4):145‐156. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. Jj Z, Dong X, Cao YY, et al. Clinical characteristics of 140 patients infected by SARS‐CoV‐2 in Wuhan, China. Allergy. 2020;267:147‐156. [DOI] [PubMed] [Google Scholar]
- 25. Cheng Y, Luo R, Wang K, et al. Kidney impairment is associated with in‐hospital death of COVID‐19 patients. medRxiv; 2020. [DOI] [PMC free article] [PubMed]
- 26. Ng M‐Y, Lee EY, Yang J, et al. Imaging profile of the COVID‐19 infection: radiologic findings and literature review. Radiology. 2020;2(1):e200034. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27. Tian S, Hu N, Lou J, et al. Characteristics of COVID‐19 infection in beijing. J Infect. 2020;467:147‐156. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28. Li Q, Guan X, Wu P, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus–infected pneumonia. N Engl J Med. 2020;382:1199‐1207. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29. Chang D, Lin M, Wei L, et al. Epidemiologic and clinical characteristics of novel coronavirus infections involving 13 patients outside Wuhan, China. JAMA. 2020;3267(3):2247‐2256. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30. Xu X‐W, Wu X‐X, Jiang X‐G, et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS‐Cov‐2) outside of Wuhan, China: retrospective case series. bmj 2020; 368. [DOI] [PMC free article] [PubMed]
- 31. Song F, Shi N, Shan F, et al. Emerging 2019 novel coronavirus (2019‐nCoV) pneumonia. Radiology. 2020;167:147‐156. 10.1148/radiol.2020200274. [DOI] [Google Scholar]
- 32. Chung M, Bernheim A, Mei X, et al. CT imaging features of 2019 novel coronavirus (2019‐nCoV). Radiology. 2020;867:147‐156. 10.1148/radiol.2020200230. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33. Wu Z, JM MG. Characteristics of and important lessons from the coronavirus disease 2019 (COVID‐19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020;3267:3247‐3256. [DOI] [PubMed] [Google Scholar]
- 34. Omrani AS, Matin MA, Haddad Q, Al‐Nakhli D, Memish ZA, Albarrak AM. A family cluster of Middle East respiratory syndrome coronavirus infections related to a likely unrecognized asymptomatic or mild case. Int J Infect Dis. 2013;17(9):e668‐e672. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35. Tsang OT‐Y, Chau T‐N, Choi K‐W, et al. Coronavirus‐positive nasopharyngeal aspirate as predictor for severe acute respiratory syndrome mortality. Emerg Infect Dis. 2003;9(11):1381‐1387. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36. Hsu L‐Y, Lee C‐C, Green JA, et al. Severe acute respiratory syndrome (SARS) in Singapore: clinical features of index patient and initial contacts. Emerg Infect Dis. 2003;9(6):713‐717. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37. Donnelly CA, Ghani AC, Leung GM, et al. Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong. Lancet. 2003;361(9371):1761‐1766. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38. Booth CM, Matukas LM, Tomlinson GA, et al. Clinical features and short‐term outcomes of 144 patients with SARS in the greater Toronto area. JAMA. 2003;289(21):2801‐2809. [DOI] [PubMed] [Google Scholar]
- 39. Varia M, Wilson S, Sarwal S, McGeer A, Gournis E, Galanis E. Investigation of a nosocomial outbreak of severe acute respiratory syndrome (SARS) in Toronto, Canada. CMAJ. 2003;169(4):285‐292. [PMC free article] [PubMed] [Google Scholar]
- 40. Loeb M. 34% mortality rate from SARS in critically ill patients at 28 days in Toronto. ACP J Club. 2004;140(1):20. [PubMed] [Google Scholar]
- 41. Peiris J, Lai S, Poon L, et al; SARS study group.Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet. 2003;361(9366):1319‐1325. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 42. Peiris JSM, Chu C‐M, Cheng VC‐C, et al. Clinical progression and viral load in a community outbreak of coronavirus‐associated SARS pneumonia: a prospective study. Lancet. 2003;361(9371):1767‐1772. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 43. Chan J, Ng C, Chan Y, et al. Short term outcome and risk factors for adverse clinical outcomes in adults with severe acute respiratory syndrome (SARS). Thorax. 2003;58(8):686‐689. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 44. Wang J‐T, Sheng W‐H, Fang C‐T, et al. Clinical manifestations, laboratory findings, and treatment outcomes of SARS patients. Emerg Infect Dis. 2004;10(5):818‐824. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45. Hon K, Leung C, Cheng W, et al. Clinical presentations and outcome of severe acute respiratory syndrome in children. Lancet. 2003;361(9370):1701‐1703. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 46. Wong K, Antonio GE, Hui DS, et al. Severe acute respiratory syndrome: radiographic appearances and pattern of progression in 138 patients. Radiology. 2003;228(2):401‐406. [DOI] [PubMed] [Google Scholar]
- 47. Singh K, Hsu L‐Y, Villacian JS, Habib A, Fisher D, Tambyah PA. Severe acute respiratory syndrome: lessons from Singapore. Emerg Infect Dis. 2003;9(10):1294‐1298. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 48. Tsang KW, Ho PL, Ooi GC, et al. A cluster of cases of severe acute respiratory syndrome in Hong Kong. N Engl J Med. 2003;348(20):1977‐1985. [DOI] [PubMed] [Google Scholar]
- 49. Ofner‐Agostini M, Gravel D, McDonald LC, et al. Cluster of cases of severe acute respiratory syndrome among Toronto healthcare workers after implementation of infection control precautions: a case series. Infect Control Hosp Epidemiol. 2006;27(5):473‐478. [DOI] [PubMed] [Google Scholar]
- 50. Zhong N, Zheng B, Li Y, et al. Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People's Republic of China, in February, 2003. Lancet. 2003;362(9393):1353‐1358. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 51. Lee N, Chan KA, Hui DS, et al. Effects of early corticosteroid treatment on plasma SARS‐associated coronavirus RNA concentrations in adult patients. J Clin Virol. 2004;31(4):304‐309. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 52. Lee N, Hui D, Wu A, et al. A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl J Med. 2003;348(20):1986‐1994. [DOI] [PubMed] [Google Scholar]
- 53. Ho P, Chau P, Yip P, et al. A prediction rule for clinical diagnosis of severe acute respiratory syndrome. Eur Respir J. 2005;26(3):474‐479. [DOI] [PubMed] [Google Scholar]
- 54. Tsui PT, Kwok ML, Yuen H, Lai ST. Severe acute respiratory syndrome: clinical outcome and prognostic correlates. Emerg Infect Dis. 2003;9(9):1064‐1069. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 55. Wong RS, Wu A, To K , et al. Haematological manifestations in patients with severe acute respiratory syndrome: retrospective analysis. BMJ. 2003;326(7403):1358‐1362. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 56. Lew TW, Kwek T‐K, Tai D, et al. Acute respiratory distress syndrome in critically ill patients with severe acute respiratory syndrome. JAMA. 2003;290(3):374‐380. [DOI] [PubMed] [Google Scholar]
- 57. Rainer TH, Cameron PA, Smit D, et al. Evaluation of WHO criteria for identifying patients with severe acute respiratory syndrome out of hospital: prospective observational study. BMJ. 2003;326(7403):1354‐1358. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 58. Wong W, Sek AC, Lau RF, et al. Accuracy of clinical diagnosis versus the World Health Organization case definition in the Amoy garden SARS cohort. Can J Emerg Med. 2003;5(6):384‐391. [DOI] [PubMed] [Google Scholar]
- 59. Zhao Z, Zhang F, Xu M, et al. Description and clinical treatment of an early outbreak of severe acute respiratory syndrome (SARS) in Guangzhou, PR China. J Med Microbiol. 2003;52(8):715‐720. [DOI] [PubMed] [Google Scholar]
- 60. Poutanen SM, Low DE, Henry B, et al; National Microbiology Laboratory, Canada; Canadian Severe Acute Respiratory Syndrome Study Team.Identification of severe acute respiratory syndrome in Canada. N Engl J Med. 2003;348(20):1995‐2005. [DOI] [PubMed] [Google Scholar]
- 61. Hung I, Cheng V, Wu A, et al. Viral loads in clinical specimens and SARS manifestations. Emerg Infect Dis. 2004;10(9):1550‐1557. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 62. Vu HT, Leitmeyer KC, Le DH, et al. Clinical description of a completed outbreak of SARS in Vietnam, February–May, 2003. Emerg Infect Dis. 2004;10(2):334‐338. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 63. Chen F, Chan K, Jiang Y, et al. In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds. J Clin Virol. 2004;31(1):69‐75. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 64. Leung C, Chiu W. Clinical picture, diagnosis, treatment and outcome of severe acute respiratory syndrome (SARS) in children. Paediatr Respir Rev. 2004;5(4):275‐288. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 65. Avendano M, Derkach P, Swan S. Clinical course and management of SARS in health care workers in Toronto: a case series. CMAJ. 2003;168(13):1649‐1660. [PMC free article] [PubMed] [Google Scholar]
- 66. Srikantiah P, Charles MD, Reagan S, et al; for the CDC SARS Clinical Investigation Team.SARS clinical features, United States, 2003. Emerg Infect Dis. 2005;11(1):135‐138. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 67. Chan KH, Poon LL, Cheng V, et al. Detection of SARS coronavirus in patients with suspected SARS. Emerg Infect Dis. 2004;10(2):294‐299. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 68. Liang W, Zhu Z, Guo J, et al; for the Beijing Joint SARS Expert Group.Severe acute respiratory syndrome, Beijing, 2003. Emerg Infect Dis. 2004;10(1):25‐31. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 69. Chen X, Zhou B, Li M, et al. Serology of severe acute respiratory syndrome: implications for surveillance and outcome. J Infect Dis. 2004;189(7):1158‐1163. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 70. C‐w L, Y‐w K, P‐w K, et al. Severe acute respiratory syndrome among children. Pediatrics. 2004;113(6):e535‐e543. [DOI] [PubMed] [Google Scholar]
- 71. Heung L, Li T, Mak S, Chan W. Prevalence of subclinical infection and transmission of severe acute respiratory syndrome (SARS) in a residential care home for the elderly. Hong Kong Med J. 2006;12(3):201‐207. [PubMed] [Google Scholar]
- 72. Tsai M‐H, Lin T‐Y, Chiu C‐H, et al. Seroprevalence of SARS coronavirus among residents near a hospital with a nosocomial outbreak. J Formos Med Assoc. 2008;107(11):885‐891. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 73. Dwosh HA, Hong HH, Austgarden D, Herman S, Schabas R. Identification and containment of an outbreak of SARS in a community hospital. CMAJ. 2003;168(11):1415‐1420. [PMC free article] [PubMed] [Google Scholar]
- 74. Ho AS, Sung JJ, Chan‐Yeung M. An outbreak of severe acute respiratory syndrome among hospital workers in a community hospital in Hong Kong. Ann Intern Med. 2003;139(7):564‐567. [DOI] [PubMed] [Google Scholar]
- 75. Grinblat L, Shulman H, Glickman A, Matukas L, Paul N. Severe acute respiratory syndrome: radiographic review of 40 probable cases in Toronto, Canada. Radiology. 2003;228(3):802‐809. [DOI] [PubMed] [Google Scholar]
- 76. Fan C‐K, Yieh K‐M, Peng M‐Y, Lin J‐C, Wang N‐C, Chang F‐Y. Clinical and laboratory features in the early stage of severe acute respiratory syndrome. J Microbiol Immunol Infect [Wei mian yu gan ran za zhi]. 2006;39(1):45‐53. [PubMed] [Google Scholar]
- 77. Choi KW, Chau TN, Tsang O. et al; Princess Margaret Hospital SARS Study Group.Outcomes and prognostic factors in 267 patients with severe acute respiratory syndrome in Hong Kong. Ann Intern Med. 2003;139(9):715‐723. [DOI] [PubMed] [Google Scholar]
- 78. Leung GM, Hedley AJ, Ho L‐M, et al. The epidemiology of severe acute respiratory syndrome in the 2003 Hong Kong epidemic: an analysis of all 1755 patients. Ann Intern Med. 2004;141(9):662‐673. [DOI] [PubMed] [Google Scholar]
- 79. Chu C‐M, Cheng VC, Hung IF, et al. Viral load distribution in SARS outbreak. Emerg Infect Dis. 2005;11(12):1882‐1886. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 80. Chu KH, Tsang WK, Tang CS, et al. Acute renal impairment in coronavirus‐associated severe acute respiratory syndrome. Kidney Int. 2005;67(2):698‐705. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 81. Jang T‐N, Yeh D, Shen S‐H, Huang C‐H, Jiang J‐S, Kao S‐J. Severe acute respiratory syndrome in Taiwan: analysis of epidemiological characteristics in 29 cases. J Infect. 2004;48(1):23‐31. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 82. T‐w W, Lee C‐k, Tam W, et al. Cluster of SARS among medical students exposed to single patient, Hong Kong. Emerg Infect Dis. 2004;10(2):269. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 83. Wang W‐K, Chen S‐Y, Liu I‐J, et al; SARS Research Group of the National Taiwan University/National Taiwan University Hospital.Detection of SARS‐associated coronavirus in throat wash and saliva in early diagnosis. Emerg Infect Dis. 2004;10(7):1213‐1219. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 84. Aburizaiza AS, Mattes FM, Azhar EI, et al. Investigation of anti–Middle East respiratory syndrome antibodies in blood donors and slaughterhouse workers in Jeddah and Makkah, Saudi Arabia, fall 2012. J Infect Dis. 2014;209(2):243‐246. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 85. Müller MA, Meyer B, Corman VM, et al. Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi Arabia: a nationwide, cross‐sectional, serological study. Lancet Infect Dis. 2015;15(5):559‐564. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 86. Alhetheel A, Altalhi H, Albarrag A, et al. Assessing the detection of middle east respiratory syndrome coronavirus IgG in suspected and proven cases of middle east respiratory syndrome coronavirus infection. Viral Immunol. 2017;30(9):649‐653. [DOI] [PubMed] [Google Scholar]
- 87. Saeed AAB, Abedi GR, Alzahrani AG, et al. Surveillance and testing for middle east respiratory syndrome coronavirus, Saudi Arabia, April 2015–February 2016. Emerg Infect Dis. 2017;23(4):682‐685. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 88. Ryu B, Cho S‐I, Oh M‐d, et al. Seroprevalence of Middle East respiratory syndrome coronavirus (MERS‐CoV) in public health workers responding to a MERS outbreak in Seoul, Republic of Korea, in 2015. Western Pac Surveill Response J. 2019;10(2):46. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 89. Ahmadzadeh J, Mobaraki K. Epidemiological status of the Middle East respiratory syndrome coronavirus in 2019: an update from January 1 to March 31, 2019. Int. J. Gen. Med. 2019;12:305‐311. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 90. Mobaraki K, Ahmadzadeh J. Current epidemiological status of Middle East respiratory syndrome coronavirus in the world from 1.1. 2017 to 17.1. 2018: a cross‐sectional study. BMC Infect Dis. 2019;19(1):351. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 91. Assiri A, Al‐Tawfiq JA, Al‐Rabeeah AA, et al. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study. Lancet Infect Dis. 2013;13(9):752‐761. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 92. Yang J‐S, Park S, Kim Y‐J, et al. Middle East respiratory syndrome in 3 persons, South Korea, 2015. Emerg Infect Dis. 2015;21(11):2084‐2087. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 93. Assiri A, McGeer A, Perl TM, et al; KSA MERS‐CoV Investigation Team.Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl Jo Med. 2013;369(5):407‐416. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 94. Assiri A, Abedi GR, Saeed AAB, et al. Multifacility outbreak of middle east respiratory syndrome in Taif, Saudi Arabia. Emerg Infect Dis. 2016;22(1):32‐40. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 95. Assiri AM, Biggs HM, Abedi GR, et al. Increase in Middle East respiratory syndrome‐coronavirus cases in Saudi Arabia linked to hospital outbreak with continued circulation of recombinant virus, July 1–August 31, 2015. Open Forum Infect Dis. 2016;267:147‐156. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 96. Halim AA, Alsayed B, Embarak S, Yaseen T, Dabbous S. Clinical characteristics and outcome of ICU admitted MERS corona virus infected patients. Egypt J Chest Dis Tuberc. 2016;65(1):81‐87. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 97. Hastings DL, Tokars JI, Aziz IZAA, et al. Outbreak of Middle East respiratory syndrome at tertiary care hospital, Jeddah, Saudi Arabia, 2014. Emerg Infect Dis. 2016;22(5):794‐801. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 98. Alhamlan F, Majumder M, Brownstein J, et al. Case characteristics among Middle East respiratory syndrome coronavirus outbreak and non‐outbreak cases in Saudi Arabia from 2012 to 2015. BMJ Open. 2017;7(1):e011865. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 99. El Bushra H, Abdalla M, Al Arbash H, et al. An outbreak of Middle East respiratory syndrome (MERS) due to coronavirus in Al‐Ahssa region, Saudi Arabia, 2015. East Mediterr Health J. 2016;22(7):467‐473. [PubMed] [Google Scholar]
- 100. Oboho IK, Tomczyk SM, Al‐Asmari AM, et al. 2014 MERS‐CoV outbreak in Jeddah—a link to health care facilities. N Engl J Med. 2015;372(9):846‐854. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 101. Kim KM, Ki M, Cho S‐i, et al. Epidemiologic features of the first MERS outbreak in Korea: focus on Pyeongtaek St. Mary's Hospital. Epidemiol Health. 2015;37:689‐695. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 102. Memish ZA, Zumla AI, Assiri A. Middle East respiratory syndrome coronavirus infections in health care workers. N Engl J Med. 2013;369(9):884‐886. [DOI] [PubMed] [Google Scholar]
- 103. Choi WS, Kang C‐I, Kim Y, et al; The Korean Society of Infectious Diseases.Clinical presentation and outcomes of Middle East respiratory syndrome in the Republic of Korea. Infect Chemother. 2016;48(2):118‐126. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 104. Al‐Abdallat MM, Payne DC, Alqasrawi S, et al. Hospital‐associated outbreak of Middle East respiratory syndrome coronavirus: a serologic, epidemiologic, and clinical description. Clin Infect Dis. 2014;59(9):1225‐1233. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 105. Saad M, Omrani AS, Baig K, et al. Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single‐center experience in Saudi Arabia. Int J Infect Dis. 2014;29:301‐306. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 106. Arabi YM, Arifi AA, Balkhy HH, et al. Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection. Ann Intern Med. 2014;160(6):389‐397. [DOI] [PubMed] [Google Scholar]
- 107. Majumder MS, Kluberg SA, Mekaru SR, Brownstein JS. Mortality risk factors for Middle East respiratory syndrome outbreak, South Korea, 2015. Emerg Infect Dis. 2015;21(11):2088‐2090. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 108. Virlogeux V, Park M, Wu JT, Cowling BJ. Association between severity of MERS‐CoV infection and incubation period. Emerg Infect Dis. 2016;22(3):526‐528. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 109. Al‐Tawfiq JA, Hinedi K, Ghandour J, et al. Middle East respiratory syndrome coronavirus: a case‐control study of hospitalized patients. Clin Infect Dis. 2014;59(2):160‐165. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 110. Alenazi TH, Al Arbash H, El‐Saed A, et al. Identified transmission dynamics of Middle East respiratory syndrome coronavirus infection during an outbreak: implications of an overcrowded emergency department. Clin Infect Dis. 2017;65(4):675‐679. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 111. Alsahafi AJ, Cheng AC. The epidemiology of Middle East respiratory syndrome coronavirus in the Kingdom of Saudi Arabia, 2012–2015. Int J Infect Dis. 2016;45:1‐4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 112. Das KM, Lee EY, Jawder SEA, et al. Acute Middle East respiratory syndrome coronavirus: temporal lung changes observed on the chest radiographs of 55 patients. Am J Roentgenol. 2015;205(3):W267‐S74. [DOI] [PubMed] [Google Scholar]
- 113. Ahmed AE. The predictors of 3‐and 30‐day mortality in 660 MERS‐CoV patients. BMC Infect Dis. 2017;17(1):615. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 114. Ahmed AE. Diagnostic delays in 537 symptomatic cases of Middle East respiratory syndrome coronavirus infection in Saudi Arabia. Int J Infect Dis. 2017;62:47‐51. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 115. Alraddadi BM, Watson JT, Almarashi A, et al. Risk factors for primary Middle East respiratory syndrome coronavirus illness in humans, Saudi Arabia, 2014. Emerg Infect Dis. 2016;22(1):49‐55. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 116. Cowling BJ, Park M, Fang VJ, Wu P, Leung GM, Wu JT. Preliminary epidemiologic assessment of MERS‐CoV outbreak in South Korea, May–June 2015. Euro Surveill. 2015;20(25):635‐643. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 117. Kang CK, Song K‐H, Choe PG, et al. Clinical and epidemiologic characteristics of spreaders of Middle East respiratory syndrome coronavirus during the 2015 outbreak in Korea. J Korean Med Sci. 2017;32(5):744‐749. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 118. Drosten C, Meyer B, Müller MA, et al. Transmission of MERS‐coronavirus in household contacts. N Engl J Med. 2014;371(9):828‐835. [DOI] [PubMed] [Google Scholar]
- 119. Feikin DR, Alraddadi B, Qutub M, et al. Association of higher MERS‐CoV virus load with severe disease and death, Saudi Arabia, 2014. Emerg Infect Dis. 2015;21(11):2029‐2035. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 120. Mohd HA, Memish ZA, Alfaraj SH, et al. Predictors of MERS‐CoV infection: a large case control study of patients presenting with ILI at a MERS‐CoV referral hospital in Saudi Arabia. Travel Med Infect Dis. 2016;14(5):464‐470. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 121. Park JW, Lee KJ, Lee KH, et al. Hospital outbreaks of middle east respiratory syndrome, Daejeon, South Korea, 2015. Emerg Infect Dis. 2017;23(6):898‐905. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 122. Sherbini N, Iskandrani A, Kharaba A, Khalid G, Abduljawad M, Hamdan A‐J. Middle East respiratory syndrome coronavirus in Al‐Madinah City, Saudi Arabia: demographic, clinical and survival data. J Epidemiol Global Health. 2017;7(1):29‐36. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 123. Adegboye OA, Gayawan E, Hanna F. Spatial modelling of contribution of individual level risk factors for mortality from Middle East respiratory syndrome coronavirus in the Arabian Peninsula. PLoS One. 2017;12(7):147‐158. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 124. Almekhlafi GA, Albarrak MM, Mandourah Y, et al. Presentation and outcome of Middle East respiratory syndrome in Saudi intensive care unit patients. Crit Care. 2016;20(1):123. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 125. Park SH, Kim Y‐S, Jung Y, et al. Outbreaks of Middle East respiratory syndrome in two hospitals initiated by a single patient in Daejeon, South Korea. Infect Chemother. 2016;48(2):99‐107. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 126. Mahase E. Covid‐19: WHO declares pandemic because of “alarming levels” of spread, severity, and inaction. BMJ. 2020;667:147‐156. [DOI] [PubMed] [Google Scholar]
- 127. Ji W, Zhang J, Bishnu G, et al. Comparison of severe and non‐severe COVID‐19 pneumonia: review and meta‐analysis. medRxiv. 2020.
- 128. Zhao Y, Zhao Z, Wang Y, Zhou Y, Ma Y, Zuo W. Single‐cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019‐nCov. BioRxiv. 2020. [DOI] [PMC free article] [PubMed]
- 129. Prompetchara E, Ketloy C, Palaga T. Immune responses in COVID‐19 and potential vaccines: lessons learned from SARS and MERS epidemic. Asian Pac J Allergy Immunol. 2020;67:105‐116. [DOI] [PubMed] [Google Scholar]
- 130. Zhou Y, Fu B, Zheng X, et al. Pathogenic T cells and inflammatory monocytes incite inflammatory storm in severe COVID‐19 patients. Natl Sci Rev. 2020;37:103‐119. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 131. Imai Y, Kuba K, Penninger JM. Angiotensin‐converting enzyme 2 in acute respiratory distress syndrome. Cell Mol Life Sci. 2007;64(15):2006‐2012. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 132. Sutton AJ, Duval S, Tweedie R, Abrams KR, Jones DR. Empirical assessment of effect of publication bias on meta‐analyses. BMJ. 2000;320(7249):1574‐1577. [DOI] [PMC free article] [PubMed] [Google Scholar]
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.
