key: cord-348821-2u6ki9dv
authors: Xu, Ping; Sun, Guo-Dong; Li, Zhi-Zhong
title: Clinical Characteristics of Two Human to Human Transmitted Coronaviruses: Corona Virus Disease 2019 versus Middle East Respiratory Syndrome Coronavirus.
date: 2020-03-10
journal: nan
DOI: 10.1101/2020.03.08.20032821
sha: 
doc_id: 348821
cord_uid: 2u6ki9dv

After the outbreak of the middle east respiratory syndrome (MERS) worldwide in 2012. Currently, a novel human coronavirus has caused a major disease outbreak, and named corona virus disease 2019 (COVID-19). The emergency of MRES-COV and COVID-19 has caused global panic and threatened health security. Unfortunately, the similarities and differences between the two coronavirus diseases remain to be unknown. The aim of this study, therefore, is to perform a systematic review to compare epidemiological, clinical and laboratory features of COVID-19 and MERS-COV population. We searched PubMed, EMBASE and Cochrane Register of Controlled Trials database to identify potential studies reported COVID-19 or MERS-COV. Epidemiological, clinical and laboratory outcomes, the admission rate of intensive cure unit (ICU), discharge rate and fatality rate were evaluated using GraphPad Prism software. Thirty-two studies involving 3770 patients (COVID-19 = 1062, MERS-COV = 2708) were included in this study. The present study revealed that compared with COVID-19 population, MERS-COV population had a higher rate of ICU admission, discharge and fatality and longer incubation time. It pointed out that fever, cough and generalised weakness and myalgia were main clinical manifestations of both COVID-19 and MERS-COV, whereas ARDS was main complication. The most effective drug for MERS-COV is ribavirin and interferon.

Coronaviruses are RNA viruses with envelope and non-segmented positive-sense, causing respiratory and intestinal tract infections in humans and other mammals [1] . Despite . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.08.20032821 doi: medRxiv preprint 4 Although many previous studies have reported clinical characteristics of COVID-19 or MERS-COV diseases [8] [9] [10] [11] , systematic comparison of clinical features between COVID-19 and MERS-COV diseases has yet been published. Thus, the purpose of this study is to perform a systematic review of epidemiological, clinical and laboratory characteristics of patients infected by COVID-19 or MERS-COV disease, and to compare COVID-19 and MERS-COV in the context of their incubation, laboratory features, admission rate of intensive cure unit (ICU) and rate of discharge and fatality, which will provide a comprehensive reference for clinical physicians in treatment of coronavirus diseases.

A comprehensive and systematic search was performed using PubMed, EMBASE and OR (2019 novel coronavirus)). If necessary, we also contacted corresponding author to obtain accurate data.

. CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.08.20032821 doi: medRxiv preprint 5 The study that met following criteria were included: (1) reporting clinical characteristics of COVID-19 or MERS-COV disease, (2) minimum sample size of five, (3) confirmed COVID-19 or MERS-COV disease, (4) English literature. Studies were excluded as following criteria: duplicate publications, case report, meta-analysis, letter, review, technology report, commentary, animal trial, correspondence, predictive study, guidence, radiograph study and meeting report.

At the beginning, 4743 potential publications were identified. We removed 678 duplicates and reviewed the titles and abstracts of remaining 4065 publications. 4015 publications were excluded for following reasons: not involved research point (n = 1378), review (n = 569), no English (n = 33), case report (n = 316), meta-analysis (n = 1), letter (n = 127), technology report (n = 196), commentaries (n = 61), animal study (n = 1107), correspondence (n = 29), predictive study (n = 110), guidence (n = 28), meeting report ( n = 16) and radiograph (n = 44). Then, a comprehensive review of full-text was conducted for remaining 50 publications. Two reviewers independently screened eligible literature, and any argument was solved by discussion with a third reviewer. Finally, thirty-two studies were included in this study . The process was shown in Figure 1 .

Two reviewers extracted independently common, clinical and laboratory characteristics of included studies, with disagreements were solved by discussion with a third reviewer. The extracted data included incubation time, white blood cell (WBC) count, lymphocyte count, creactive protein (CRP), alamine aminotransferase (ALT), aspartate aminotransferase (AST), . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.08.20032821 doi: medRxiv preprint 6 creatinine, creatine kinase (CK), the admission rate of intensive cure unit (ICU), rate of discharge and fatality, symptom, comorbidity, complications and cure rate of drug. For normality distribution data, outcomes were extracted directly. For skewness distribution data, the outcomes was extracted after being converted as specific formula [40] .

The quality assessment of included studies was performed through the Newcastle-Ottawa Quality Assessment Scale (NOS), as recommended by the Cochrane Non-Randomized

Studies [41] . The NOS includes three parts for risk of bias, with nine points in total: (1) selection of research groups (four points); (2) inter-group comparability (two points); and (3) ascertainment of exposure and outcomes (three points) for case-control and cohort studies, respectively. Study that scored 6 or more was qualified for systematic review [42] . The assessment process was completed by two reviewers independently. All debates were solved by discussion with a third reviewer.

All statistical analyses and graphs were generated and plotted using GraphPad Prism version 7.00 software (GraphPad Software Inc). The p value < 0.05 suggests significant difference.

All included studies were retrospective study . Among ten studies reported COVID-19, one trial was performed in Netherlands [12] and remaining nine trials were conducted in China [8-9, 13-16, 37-39] . The sample size ranged from 6 to 425, and had a total . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

is the (which was not peer-reviewed) The copyright holder for this preprint [24-26, 31, 33] , one trial was performed in Iran [19] and one trial was conducted in Japan [10] . The sample size ranged from 5 to 883, and had a total of 2708 patients. The year of publications ranged from 2013 to 2020. Clinical and laboratory characteristics of included study were shown in Table 1 and Table 2 respectively.

Among thirty-two included studies, four studies obtained 6 points of NOS [26, 28, 32, 35] , and remaining twenty-eight studies obtained 7 points of NOS or more [8-25, 27, 29-31, 33-34, 36-39] . The result of quality assessment was presented in Table 3 .

For COVID-19 population, the number of patients with fever was 480 (45.2%), cough was 373 (35.1%), generalised weakness and myalgia was 318 (29.9%), stuffy or rhinorrhoea was 6 (0.6%), pharyngalgia was 32 (3%), chest pain was 10 (0.9%), diarrhoea or anorexia was 123 (11.6%), dyspnoea was 140 (13.2%) and dizziness or headache was 60 (5.6%). For MERS-COV population, the amount of patients with fever was 404 (14.9%), cough was 424 (15.7%), generalised weakness and myalgia was 337 (12.4%), stuffy or rhinorrhoea was 17 (0.6%), pharyngalgia was 47 (1.7%), chest pain was 27 (1%), diarrhoea or anorexia was 128 (4.7%), dyspnoea was 271 (10%) and dizziness or headache was 131 (4.8%). The Above results were shown in Table 4 .

For COVID-19 population, the main complications included shock, arrhythmia, acute respiratory distress syndrome (ARDS), acute cardiac injury, acute kidney injury and acute . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.08.20032821 doi: medRxiv preprint liver injury, and the amount of which was 17 (1.6%), 28 (2.6%), 51 (4.8%), 11 (1%), 10 (0.9%) and 2 (0.2%) respectively. For MERS-COV population, the number of individuals presented shock was 22 (0.8%), arrhythmia was 11 (0.4%), ARDS was 83 (3.1%), acute cardiac injury 10 (0.4%), acute kidney injury was 30 (1.1%), acute liver injury was 22 (0.8%) and neurological symptoms was 4 (0.1%). The results were shown in Table 5 . Table 6 .

Systematic review was performed for clinical and laboratory outcomes of coronavirus disease. There was no significant difference in age (50.9 ± 2 vs. 53.6 ± 1.5, P = 0.3), WBC Table 7 .

. CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.08.20032821 doi: medRxiv preprint

The higher admission rate of ICU was found in MERS-COV population than in COVID-19 population ( 43.6% vs. 22.4%, Figure 2 ). There was a higher discharge rate in MERS-COV populations compared with COVID-19 population ( 59.9% vs. 33.5%, Figure 3 ). The lower fatality rate was found in COVID-19 population compared with MERS-COV population (6.8% vs. 34.1%, Figure 4 ). 

Coronavirus is an important pathogen causing respiratory and intestinal infection. Of seven identified coronaviruses, the two very pathogenic viruses, SARS-COV and MERS-COV, cause severe ARDS and even acute respiratory failure. With a mortality rate of more than 10% and more than 35% respectively [43] [44] . The four other human coronaviruses In addition, we found that the number of males is more than that of females in either COVID-19 or MERS-COV population. The possible reason of reduced susceptibility of females to viral infection is that females have a lot of X chromosome and estrogen that are vital components in development of innate and adaptive immunity [47] . Meanwhile, numbers of patients with COVID-19 infection had chronic comorbidities, mainly hypertension, diabetes and cardiovascular disease, which is similar to MERS-COV population. Those results indicate that older adult males with chronic underlying disease might be more susceptibility to COVID-19 or MERS-COV.

. CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.08.20032821 doi: medRxiv preprint 1 1 In terms of laboratory testing, reduced lymphocytes and increased CRP were found in both COVID-19 and MERS-COV patients. This result indicates that COVID-19 might be associated with cellular immune response, mainly act on lymphocytes like MERS-COV does [48] . The cells infected by viruses induce the release of numbers of pro-inflammatory cytokines and inflammation storm in the body. Moreover, increased cytokines might make damage to related organs such as liver [49] . Our results demonstrated that abnormal value of AST was found in MERS-COV population, but not in COVID-19 population. The possible reason is that the follow-up time of COVID-19 population was too short, and the liver might remain to be in compensatory stage. For this result, a long follow-up time study is urgently needed. On the other hand, our results suggested that MERS-COV population had a higher rate of ICU admission and fatality than COVID-19 population, indicating that compared with MERS-COV, COVID-19 has less toxic and more easily cured. However, lower discharge rate was found in COVID population than in MERS-COV population. The possible explanation is that most of COVID-19 patients remained to be hospitalized at the time of manuscript submission, and data on those patients could not be obtained in time. Thus, careful interpretation is urged for this result.

Up to now, no effective strategy has been found for treatment of COVID-19 infection [50] . Currently, the measure to COVID-19 is to control the source of the infection; taking personal protective works to reduce the risk of transmission; and early diagnosing, isolating and supportive treating for confirmed patients. In the present study, our systematic results of cure rate of drug for MERS-COV infection indicated that ribavirin and interferon, oseltamivir, antivirals and intravenous immunoglobulin all had been effective for MERS-COV infection, with the cure rate of those drugs was 74.2%, 69.2%, 67.1% and 62.5% respectively. Thus, we . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.08.20032821 doi: medRxiv preprint 1 2 assume that those drugs might also be effective at COVID-19 infection. However, further studies are needed to confirm this idea.

This study has several limitations. First, many patients infected by COVID-19 remained to be hospitalized at the time of manuscript submission, leading to the unavailable of some data. Second, the follow-up time of COVID-19 population is too short to get related data from long-term observations of this disease. Third, finding of statistical tests and p values between COVID-19 and MERS-COV populations should be interpreted with caution. Fourth, the number of MERS-COV patients treated by drugs is small, careful understanding is needed for the cure rate of drug for this disease. Finally, as COVID-19 is still developing around the world and remains to have many unknowns, the results of this study are staged and need to be carefully understood. More large-sample, multicentre, high-quality research should be performed to update this study.

Our systematic review reveals that main clinical manifestations of both COVID-19 and MERS-COV populations are fever, cough and generalised weakness and myalgia. ARDS is main complication of both two populations. COVID-19 population has a shorter incubation time and lower rate of ICU admission, discharge and fatality compared with MRES-COV population.

This study was supported by grants from the National Natural Science Foundation of China (Nos.31970862) and Guangzhou Municipal Science and Technology project (Nos.

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is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.08.20032821 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.08.20032821 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.08.20032821 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.08.20032821 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

is the (which was not peer-reviewed) The copyright holder for this preprint . https://doi.org/10.1101/2020.03.08.20032821 doi: medRxiv preprint

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