Liver function tests profile in COVID-19 patients at the admission time: A systematic review of literature and conducted researches
Azadeh Laali1, Alireza Tabibzadeh2, Maryam Esghaei2, Parastoo Yousefi2, Saber Soltani3, Hossein Ajdarkosh4, Alireza Mosavi-Jarrahi5, Mohamad Hadi Karbalaie Niya4
1 Department of Infectious Diseases, Firouzgar Hospital, Iran University of Medical Sciences, Tehran, Iran
2 Department of Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
3 Department of Virology, Faculty of Public Health, Tehran University of Medical Sciences, Tehran, Iran
4 Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
5 School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
|Date of Submission||06-Apr-2020|
|Date of Acceptance||28-Jun-2020|
|Date of Web Publication||23-Dec-2020|
Dr. Mohamad Hadi Karbalaie Niya
Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran
Source of Support: None, Conflict of Interest: None
Background: Since the start of coronavirus epidemic in Wuhan, China, in early December 2019, many literatures addressed its epidemiology, virology, and clinical presentation. In this review, we systematically reviewed the published literature in the field of liver function tests profile in COVID-19 patients at the admission time. Materials and Methods: systematic literature search were performed in EMBASE, PubMed, Science Direct, and Scopus using “severe acute respiratory syndrome 2 coronavirus (SARS-CoV-2)”, “SARS,” “SARS-CoV,” “coronavirus,” “novel coronavirus,” “liver,” “hepatitis,” “Liver function” keywords. The search was limited to range from 2019 to May 19, 2020. Results: From a total 7298 articles, 145 were screened and 18 were eligible for further analysis. The highest rate of liver associated comorbidities was reported 11%. The aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were the most frequent assessed enzymes. Increase in AST level was seen in 10%–53% of patients while The ALT increase was seen in 5%–28% of COVID-19 patients at the admission time. The prothrombin time was increase in 7%–12% of patients and the D-dimer was reports increase in 14%–36% of COVID-19 patients at the admission time. Furthermore, albumin decrease was seen in 6%–98% of COVID-19 patients at the admission time. Conclusion: In conclusion, by using the results of study, it could be suggested that the liver function tests assessment is critical assessment in COVID-19 patients at the admission time. This liver function test could be used as potential prognostic factor in COVID-19 severity in future.
Keywords: COVID-19, liver function tests, liver, SARS-CoV-2, systematic review
|How to cite this article:|
Laali A, Tabibzadeh A, Esghaei M, Yousefi P, Soltani S, Ajdarkosh H, Mosavi-Jarrahi A, Karbalaie Niya MH. Liver function tests profile in COVID-19 patients at the admission time: A systematic review of literature and conducted researches. Adv Biomed Res 2020;9:74
|How to cite this URL:|
Laali A, Tabibzadeh A, Esghaei M, Yousefi P, Soltani S, Ajdarkosh H, Mosavi-Jarrahi A, Karbalaie Niya MH. Liver function tests profile in COVID-19 patients at the admission time: A systematic review of literature and conducted researches. Adv Biomed Res [serial online] 2020 [cited 2021 Apr 14];9:74. Available from: https://www.advbiores.net/text.asp?2020/9/1/74/304368
| Introduction|| |
Coronaviridae members are enveloped viruses with the RNA genome length 26–32 Kilo base and causative agent for respiratory and enteric infections in animals and humans. The name coronavirus mentions to the envelope spikes which presents virus-specific morphology. In human host, the coronaviruses infect respiratory and enteric cells. This infection manifestation could be range as asymptomatic, self-limiting to sever bronchitis and pneumonia with renal complications. Coronaviridae classified as Nidovirales order, Coronavirinae subfamily and includes Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus genera. The Alphacoronavirus and Betacoronavirus are causative agent for respiratory human infections and animals enteric infection while the Gammacoronavirus and Deltacoronavirus genera mostly associated with birds. In human hosts with a competent immune system HCoV-NL-63, HCoV-229E, HCoV-OC43, and HKU-1 cause mild upper respiratory infections, while highly pathogenic coronaviruses such as MERC-CoV and severe acute respiratory syndrome coronavirus (SARS-CoV) can induce severe respiratory diseases., HCoV-229E and HCoV-OC43 are responsible for 15%–29% of the common colds cases. These two viruses are known as prototypes of the Alphacoronavirus and Betacoronavirus, respectively. The Alphacoronavirus and Betacoronavirus genus includes some emerging viruses in animals which can cause the economical lost.,, The origin of the HCoV-229E, HCoV-OC43, MERC-CoV, and SARS-CoV are bats while the HCoV-OC43 and HKU-1 origin seems to be rodents., Domestic animals could be important in the transmission of coronaviruses due to their role as intermediate hosts.,,, It could be assumed that, the major reservoir for the Alphacoronaviruses are bats. Frist reported emerging coronavirus was seen in 2002–2003 in Guangdong, China. This virus named as SARS-CoV and causes an epidemic condition worldwide. After a decade, the MERS-CoV in 2012 introduce as new epidemic virus from the Middle East and UKA (the United Kingdome Arabia). In the SARS-CoV epidemy, the Civet cats transmitted the virus to the human population.,,, Further investigations indicated these civet cats were infected from other animal sources., These investigations leads to finding a group of Betacoronavirus named as SARS-like coronaviruses or SARS-CoV-related coronaviruses in horseshoe or genus Rhinolophus bats. The assessment of these bats shows that the horseshoe bats are the natural reservoir and civet cats are intermediate host for SARS-CoV.,,
In December 30, 2019, pneumonia with an unknown etiology was seen in sea food market Wuhan, China. By December 31, 2019, 27 cases of pneumonia with unexplained cause were reported. This condition leads to 41 cases of 2019-novel coronavirus (2019-nCoV) (which later rename as SARS-COV-2) by January 2, 2020. First death by the virus reported in January 11, 2020, in a 61-year-old male with abdominal tumors and chronic liver disease.
Further investigations leads to the, sequencing of the virus genome, reporting first case in other countries, first case in the USA and number of infected people and number of mortality by the WHO. Furthermore, in January 30, 2020, this virus introduce as Public Health Emergency of International Concern by the WHO. Since the January 2020, there are a great number of scientific publications about the SARS-COV-2 virological features, disease and epidemic condition.
COVID-19 patients show different symptoms, these symptoms are includes fever, headache, cough, and other respiratory symptoms. Regardless of respiratory symptoms COVID-19 patients shows gastro intestinal symptoms such as diarrhea, nausea, and liver damage symptoms., The angiotensin-converting enzyme 2 (ACE-2) introduced as cell receptor for SARS-CoV-2 attachment and infectivity. The tissue distribution of ACE-2 in bile duct epithelial cells suggested a possible tropism for virus to the liver. There are verities of liver function presentation in COVID-19 patients. In this review, we systematically reviewed the published literature in the field of liver function tests profile in COVID-19 patients at the admission time.
| Materials and Methods|| |
The conducted studies were obtained using systematic literature search. Systematic search was performed in EMBASE, PubMed, Science Direct, Scopus, and relevant studies in Google scholar using “SARS-CoV-2,” “SARS,” “SARS-CoV,” “coronavirus,” “ nCoV,” “liver,” “hepatitis,” “Liver function” keywords. The search was limited to the range from 2019 to May 19, 2020. Furthermore, for preventing the narrowing due to the limited date range and number of studies we used the “OR” between all of keywords in search query. The search strategy flow chart is illustrated in [Figure 1].
|Figure 1: The search strategy flow chart for conducted research in liver function tests in COVID-19 patients|
Click here to view
Inclusion criteria were including all of relevant studies which there are extractable results about liver function tests profile includes aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin (ALB), gamma- glutamyltransferase (GGT), alkaline phosphatase (ALP), prothrombin time (PT), and D-dimer in COVID-19 patients at the admission time. Furthermore, all relevant original studies in all of the study settings were assessed for the relevance to the current study subject.
Literature review on scientific publications
The relevant studies were listed in endnote Version X7 (Thomson Reuters) and met the inclusion criteria. The screening and data extraction were conducted by two independent authors. The data extraction from records was including first author's name, liver function tests profile, gender, and sample size.
| Results|| |
Search result and severe acute respiratory syndrome coronavirus-2 patients
Conducted search using the mentioned keywords leads to the 7298 documents. After the screening of the documents based on the title and abstract 145 documents were selected. Further investigations based on the study strings and full text leads to 18 original research articles in the field of liver function tests profile in COVID-19 patients at the admission time. By the assessment of 18 included studies, the mean age of patients was ranged from 47 to 56 years. In different studies, the male gender portion of patients was ranged from 40% to 73%. Different studies reports different conditions about the comorbidities. The highest rate of liver associated comorbidities was reported 11%. The demographic and laboratory extracted data from 18 studies are listed in [Table 1].
|Table 1: The extracted data from 18 included articles for liver function tests in coronavirus disease-2019 patients|
Click here to view
Liver function tests profile in COVID-19 patients
The AST and ALT were the most frequent assessed enzymes. By the assessment of all 18 included studies, the lowest and highest AST reported levels were 6 and 107 U/L, respectively. The mean AST level in COVID-19 patients was ranged from 21 to 40 U/L. In the 16 studies, the up regulation of the AST in COVID-19 patients at the time of the admission was reported and this increase in AST level was seen in 10%–53% of COVID-19 patients. In addition, the maximum and minimum reported values for ALT were 115 and 13, respectively. Mean ALT level at the admission time was ranged from 18 to 46 in COVID-19 patients. The ALT up regulation was reported in 14 different studies. The ALT increase was seen in 5%–28% of COVID-19 patients at the admission time. Furthermore, the GGT and ALP were assessed in limited number of studies. By considering 5 studies in the field of GGT assessment, the GGT levels were increased in 12%–17% of COVID-19 patients at the admission time and mean GGT level was 36 to 45 U/L. In addition, the ALP was reported to be increased in COVID-19 patients in 4 individual studies and the maximum ALP level was 144 U/L in assessed studies [Table 1].
The PT and D-dimer were the most important coagulation tests in COVID-19 patients. The PT results were reports increase in 7 individual studies in 7%–12% of the COVID-19 patients at the admission time. The mean PT time in COVID-19 patients was 10–13.5 seconds. In addition, the D-dimer value was ranged from 0.2 to 1.97 mg/L in 10 studies. Maximum D-dimer level was reports 3.7 in COVID-19 patients at the admission time. The D-dimer was reports increase in 14%–36% of COVID-19 patients at the admission time [Table 1].
Albumin and total bilirubin
Another important marker for COVID-19 patients seems to be the decrease in ALB level. The ALB decrease was seen in 6%–98% of COVID-19 patients at the admission time in different studies. The total bilirubin level seems to be increase in 5%–21% of the COVID-19 patients at the admission time. By the assessment of all 6 studies for total bilirubin assessment, the lowest and highest bilirubin reported levels were 6 and 46 g/L, respectively [Table 1].
| Discussion|| |
Acute respiratory infections are caused by different microbial agents which need to mention that 80% of acute respiratory infections are due to the viruses. Accurate and rapid diagnosis of viral respiratory infections is essential for prescribe appropriate treatment prevent epidemics and even pandemics conditions. Antibiotics use cases are also reduced by the correct detection and distinguish of viral infections from other pathogens such as bacteria. Virus culture and IFA are two of the most common methods for detecting viruses, but time consuming. Furthermore, highly sensitive methods such as nucleic acid amplification tests and point-of-care tests could be useful. Common tests for the detection of coronaviruses include reverse transcription polymerase chain reaction (RT-PCR), real-time RT PCR, RT loop-mediated isothermal amplification (RT-LAMP), and RT-LAMP.,,,, Another approach used is RT-LAMP, which identifies the N gene and the ORF1a gene region without cross-reactivity with other viruses. One of the most important and priorities in the outbreak of an infectious agent is an early reliable diagnosis. The RT-PCR is common method for detection viral agents in respiratory secretions. Some studies have shown that collaboration between public and academic laboratories and the use of real time-PCR method can be lead to a strong diagnosis of viral isolates based on defined protocols at the time of international emergencies.,,,,,, With the outbreak of the nCoV respiratory infection, the virus genome was reported on January 10 by community online resource virological.org “Wuhan-Hu-1, GenBank accession number MN908947” for immediate health support. In the following, four sequences genome was sequenced on January 12 in the Sharing All Influenza Data (GISAID). Initial diagnostic methods revealed that the nCoV genome was very similar to the SARS coronavirus the causative of the outbreak on 2002–2003 among human populations.
Regardless of respiratory syndromes, COVID-19 patients could face with a verity of symptoms include liver damage symptoms. Conducted researches, suggested that the expression of the ACE-2 in bile duct epithelial cells could be important in liver pathogenesis of the SARS-CoV-2 in COVID-19 patients. In addition, conducted research in SARS-CoV shows virus particles in liver and hepatic vascular cells in autopsies samples. In conducted study by Wang et al. the patients data analysis shows that the abnormality in liver enzymes is associated with disease severity. In addition, Cai et al. finding suggested same results about the severity of the disease in COVID-19 patients. These results could indicate the importance of the liver enzyme assessment in the COVID-19 at the admission time as prognostic factor for further therapeutic actions. Regardless of liver function at the admission time, Fan et al. show that in mean range of 7 to 11 days after the admission the liver enzymes were elevated in COVID-19 patients. Which it could represents the disease progression or the treatment related liver injuries. In addition, conducted research by Zhang et al. indicated that the liver enzymes in COVID-19 patients are statistically significant higher than community acquired pneumonia patients. These findings highlighted that importance of the liver function assessment in COVID-19 patients. By considering all these research about the liver associated pathogenesis of COVID-19, a conducted study by Hong et al. introduced a case of liver transplantation from SARS-CoV-2-infected donor to an un infected patient. In this study, the liver donor-derived transmission of SARS-CoV-2 through the liver recipient was not seen. This finding could be in conflict with SARS-CoV-2 transmission through the organ donation. However, this matter needs further investigation. It should be noted that, the major limitation in our study was the limitation of the included studies which it makes hard to concludes a clear results. Furthermore, the advantage of the current study in compare with all other studies in the field of liver function and pathogenesis in COVID-19 patients are a comprehensive search, focusing in liver enzymes, and coagulation markers range and numerical results and including the patients' data from the admission time.
In 2002, when SARS-CoV was first time reported or the MERS-CoV in 2012,, there are no licensed vaccines toward the prevention or specific treatment against the MERS-CoV infection, and the current treatments are symptomatic, supportive or nonspecific antiviral treatment., In this state, antiviral drug resistance is not out of the question. It can assumed that, the knowledge gained from the two previous outbreaks of SARS-CoV and MERS-CoV will be helpful for therapies approaches to the 2019 nCoV (SARS-CoV-2). For instance, combined treatment approaches for MERS-CoV include the use of convalescent sera, anti-inflammatory drugs such as corticosteroids, interferon, ribavirin, and protease inhibitors.,,, However, other studies have also investigated various in vitro antiviral agents that had promising results and are still expanding., There are verities of conducted research in the field of the possible therapeutic options for COVID-19 around the world. In should be noted that, some of this treatments are associated with liver damage in COVID-19 patients. In the conducted study by Cai et al., some of the patients show a liver damage during hospitalization and treatment. This finding suggested the importance of the liver function test monitoring during the COVID-19 patients.
| Conclusion|| |
By using the results of study, it could be suggested that the liver function testes assessment is critical assessment in COVID-19 patients at the admission time. This liver function test could be used as potential prognostic factor in COVID-19 severity in future. The liver function tests assessment should be considered as important matter during COVID-19 patients' treatment. By the considering the importance of the liver enzyme assessment in COVID-19 patients, this filed clearly needs further investigations.
This study supported by the grant of Iran University of Medical Sciences, Tehran, Iran by the code no: 98-4-30-17490.
Financial support and sponsorship
This study was supported by Iran University of Medical Sciences, Tehran, Iran.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Lai MM, Cavanagh D. The molecular biology of coronaviruses. In: Advances in Virus Research. Vol. 48. Academic Press; 1997. p. 1-100.
Wevers BA, van der Hoek L. Recently discovered human coronaviruses. Clin Lab Med 2009;29:715-24.
Woo PC, Lau SK, Lam CS, Lau CC, Tsang AK, Lau JH, et al
. Discovery of seven novel Mammalian and avian coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus. J Virol 2012;86:3995-4008.
Su S, Wong G, Shi W, Liu J, Lai ACK, Zhou J, et al
. Epidemiology, genetic recombination, and pathogenesis of coronaviruses. Trends Microbiol 2016;24:490-502.
Forni D, Cagliani R, Clerici M, Sironi M. Molecular evolution of human coronavirus genomes. Trends Microbiol 2017;25:35-48.
Monto AS. Medical reviews. Coronaviruses. Yale J Biol Med 1974;47:234-51.
Brian D, Baric R. Coronavirus genome structure and replication. Coronavirus replication and reverse genetics: Springer; 2005. p. 1-30.
Lin CM, Saif LJ, Marthaler D, Wang Q. Evolution, antigenicity and pathogenicity of global porcine epidemic diarrhea virus strains. Virus Res 2016;226:20-39.
Zhou P, Fan H, Lan T, Yang XL, Shi WF, Zhang W, et al
. Fatal swine acute diarrhoea syndrome caused by an HKU2-related coronavirus of bat origin. Nature 2018;556:255-8.
Huang YW, Dickerman AW, Piñeyro P, Li L, Fang L, Kiehne R, et al
. Origin, evolution, and genotyping of emergent porcine epidemic diarrhea virus strains in the United States. mBio 2013;4:e00737-13.
Liu C, Tang J, Ma Y, Liang X, Yang Y, Peng G, et al
. Receptor usage and cell entry of porcine epidemic diarrhea coronavirus. J Virol 2015;89:6121-5.
Simas PV, Barnabé AC, Durães-Carvalho R, Neto DF, Caserta LC, Artacho L, et al
. Bat coronavirus in Brazil related to appalachian ridge and porcine epidemic diarrhea viruses. Emerg Infect Dis 2015;21:729-31.
Lacroix A, Duong V, Hul V, San S, Davun H, Omaliss K, et al
. Genetic diversity of coronaviruses in bats in Lao PDR and Cambodia. Infect Genet Evol 2017;48:10-8.
Zhong N, Zheng B, Li Y, Poon L, Xie Z, Chan K, et al
. Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People's Republic of China, in February, 2003. Lancet 2003;362:1353-8.
Reusken CB, Haagmans BL, Müller MA, Gutierrez C, Godeke GJ, Meyer B, et al
. Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: A comparative serological study. Lancet Infect Dis 2013;13:859-66.
Guan Y, Zheng BJ, He YQ, Liu XL, Zhuang ZX, Cheung CL, et al
. Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China. Science 2003;302:276-8.
Kan B, Wang M, Jing H, Xu H, Jiang X, Yan M, et al
. Molecular evolution analysis and geographic investigation of severe acute respiratory syndrome coronavirus-like virus in palm civets at an animal market and on farms. J Virol 2005;79:11892-900.
Tu C, Crameri G, Kong X, Chen J, Sun Y, Yu M, et al
. Antibodies to SARS coronavirus in civets. Emerg Infect Dis 2004;10:2244-8.
Song HD, Tu CC, Zhang GW, Wang SY, Zheng K, Lei LC, et al
. Cross-host evolution of severe acute respiratory syndrome coronavirus in palm civet and human. Proc Natl Acad Sci U S A 2005;102:2430-5.
Lau SK, Woo PC, Li KS, Huang Y, Tsoi HW, Wong BH, et al
. Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats. Proc Natl Acad Sci U S A 2005;102:14040-5.
Yang L, Wu Z, Ren X, Yang F, He G, Zhang J, et al
. Novel SARS-like betacoronaviruses in bats, China, 2011. Emerg Infect Dis 2013;19:989-91.
He B, Zhang Y, Xu L, Yang W, Yang F, Feng Y, et al
. Identification of diverse alphacoronaviruses and genomic characterization of a novel severe acute respiratory syndrome-like coronavirus from bats in China. J Virol 2014;88:7070-82.
Jacob L, Smith L, Butler L, Barnett Y, Grabovac I, McDermott D, et al
. COVID-19 social distancing and sexual activity in a sample of the British Public. J Sex Med 2020; 12:1229-36.
Hernández A, Papadakos PJ, Torres A, González DA, Vives M, Ferrando C, et al
. Dos terapias conocidas podrían ser efectivas como adyuvantes en el paciente crítico infectado por COVID-19. Rev Española de Anestesiol Reanimación 2020;67:245-52.
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al
. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506.
Lomoro P, Verde F, Zerboni F, Simonetti I, Borghi C, Fachinetti C, et al
. COVID-19 pneumonia manifestations at the admission on chest ultrasound, radiographs, and CT: Single-center study and comprehensive radiologic literature review. Eur J Radiol Open 2020;7:100231.
Hui DS, I Azhar E, Madani TA, Ntoumi F, Kock R, Dar O, et al
. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health-The latest 2019 novel coronavirus outbreak in Wuhan, China. Int J Infect Dis 2020;91:264-6.
Cheng VC, Wong SC, To KK, Ho P, Yuen KY. Preparedness and proactive infection control measures against the emerging Wuhan coronavirus pneumonia in China. J Hospital Infect 2020;104(3):254-5.
Peng S, Huang L, Zhao B, Zhou S, Braithwaite I, Zhang N, et al
. Clinical course of coronavirus disease 2019 in 11 patients after thoracic surgery and challenges in diagnosis. J Thorac Cardiovasc Surg 2020;160:585-92.
Turkistani KA. Precautions and recommendations for orthodontic settings during the COVID-19 outbreak: A review. Am J Orthod Dentofacial Orthop 2020.
Fan Z, Chen L, Li J, Cheng X, Yang J, Tian C, et al
. Clinical Features of COVID-19-Related Liver Damage. Clin Gastroenterol Hepatol 2020;18:1561-66.
Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al
. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708-20.
Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al
. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020;579:270-3.
Chai X, Hu L, Zhang Y, Han W, Lu Z, Ke A, et al
. Specific ACE2 expression in cholangiocytes may cause liver damage after 2019-nCoV infection. BioRxiv. 2020.
Feng G, Zheng KI, Yan QQ, Rios RS, Targher G, Byrne CD, et al
. COVID-19 and liver dysfunction: Current insights and emergent therapeutic strategies. J Clin Transl Hepatol 2020;8:18-24.
Wang Y, Liu S, Liu H, Li W, Lin F, Jiang L, et al
. SARS-CoV-2 infection of the liver directly contributes to hepatic impairment in patients with COVID-19. J Hepatol 2020.
Cai Q, Huang D, Yu H, Zhu Z, Xia Z, Su Y, et al
. COVID-19: Abnormal liver function tests. J Hepatol 2020;72:1864-72.
Sun Y, Dong Y, Wang L, Xie H, Li B, Chang C, et al
. Characteristics and prognostic factors of disease severity in patients with COVID-19: The Beijing experience. J Autoimmun 2020; Apr 24:102473.
Zhang Y, Zheng L, Liu L, Zhao M, Xiao J, Zhao Q. Liver impairment in COVID-19 patients: A retrospective analysis of 115 cases from a single centre in Wuhan city, China. Liver Int 2020;40:2095-103.
Pan L, Mu M, Yang P, Sun Y, Wang R, Yan J, et al
. Clinical characteristics of COVID-19 patients with digestive symptoms in Hubei, China: A descriptive, cross-sectional, multicenter study. Am J Gastroenterol 2020;115:766-73.
Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al
. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet 2020;395:507-13.
Xu XW, Wu XX, Jiang XG, Xu KJ, Ying LJ, Ma CL, 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:???.
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al
. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet 2020;395:1054-62.
Shi H, Han X, Jiang N, Cao Y, Alwalid O, Gu J, et al
. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: A descriptive study. Lancet Infect Dis 2020;20:425-34.
Chen J, Qi T, Liu L, Ling Y, Qian Z, Li T, et al
. Clinical progression of patients with COVID-19 in Shanghai, China. J Infect 2020;80:e1-e6.
Huang Y, Tu M, Wang S, Chen S, Zhou W, Chen D, et al
. Clinical characteristics of laboratory confirmed positive cases of SARS-CoV-2 infection in Wuhan, China: A retrospective single center analysis. Travel Med Infect Dis 2020;Feb 27:101606.
Qian GQ, Yang NB, Ding F, Ma AHY, Wang ZY, Shen YF, et al
. Epidemiologic and Clinical Characteristics of 91 Hospitalized Patients with COVID-19 in Zhejiang, China: A retrospective, multi-centre case series. QJM 2020;113:474-81.
Yang W, Cao Q, Qin L, Wang X, Cheng Z, Pan A, et al
. Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19): A multi-center study in Wenzhou city, Zhejiang, China. J Infect 2020;80:388-93.
Wan S, Xiang Y, Fang W, Zheng Y, Li B, Hu Y, et al
. Clinical features and treatment of COVID-19 patients in northeast Chongqing. J Med Virol 2020; 92: 797– 806.
Jin X, Lian JS, Hu JH, Gao J, Zheng L, Zhang YM, et al
. Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms. Gut 2020;69:1002-9.
Mahony JB, Petrich A, Smieja M. Molecular diagnosis of respiratory virus infections. Crit Rev Clin Lab Sci 2011;48:217-49.
Zhang N, Wang L, Deng X, Liang R, Su M, He C, et al
. Recent advances in the detection of respiratory virus infection in humans. J Med Virol 2020;92:408-17.
Azar MM, Landry ML. Detection of influenza A and B viruses and respiratory syncytial virus by use of clinical laboratory improvement amendments of 1988 (CLIA)-waived point-of-care assays: A paradigm shift to molecular tests. J Clin Microbiol 2018;56:e00367-18.
Wang N, Luo C, Liu H, Yang X, Hu B, Zhang W, et al
. Characterization of a new member of alphacoronavirus with unique genomic features in rhinolophus bats. Viruses 2019;11:379.
Bhadra S, Jiang YS, Kumar MR, Johnson RF, Hensley LE, Ellington AD. Real-time sequence-validated loop-mediated isothermal amplification assays for detection of Middle East respiratory syndrome coronavirus (MERS-CoV). PLoS One 2015;10:e0123126.
Chan JF, Choi GK, Tsang AK, Tee KM, Lam HY, Yip CC, et al
. Development and evaluation of novel real-time reverse transcription-PCR assays with locked nucleic acid probes targeting leader sequences of human-pathogenic coronaviruses. J Clin Microbiol 2015;53:2722-6.
Lu X, Whitaker B, Sakthivel SK, Kamili S, Rose LE, Lowe L, et al
. Real-time reverse transcription-PCR assay panel for Middle East respiratory syndrome coronavirus. J Clin Microbiol 2014;52:67-75.
Shirato K, Yano T, Senba S, Akachi S, Kobayashi T, Nishinaka T, et al
. Detection of Middle East respiratory syndrome coronavirus using reverse transcription loop-mediated isothermal amplification (RT-LAMP). Virol J 2014;11:139.
Shirato K, Semba S, El-Kafrawy SA, Hassan AM, Tolah AM, Takayama I, et al
. Development of fluorescent reverse transcription loop-mediated isothermal amplification (RT-LAMP) using quenching probes for the detection of the Middle East respiratory syndrome coronavirus. J Virol Methods 2018;258:41-8.
Corman VM, Eckerle I, Bleicker T, Zaki A, Landt O, Eschbach-Bludau M, et al
. Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction. Euro Surveill 2012;17:20285.
Abbott A. SARS testing: First past the post. Nature 2003;423:114.
Corman VM, Müller MA, Costabel U, Timm J, Binger T, Meyer B, et al
. Assays for laboratory confirmation of novel human coronavirus (hCoV-EMC) infections. Euro Surveill 2012;17:20334.
Drosten C, Günther S, Preiser W, van der Werf S, Brodt HR, Becker S, et al
. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med 2003;348:1967-76.
Corman VM, Eickmann M, Landt O, Bleicker T, Brünink S, Eschbach-Bludau M, et al
. Specific detection by real-time reverse-transcription PCR assays of a novel avian influenza A (H7N9) strain associated with human spillover infections in China. Euro Surveill 2013;18:20461.
Panning M, Charrel RN, Donoso Mantke O, Landt O, Niedrig M, Drosten C. Coordinated implementation of chikungunya virus reverse transcription-PCR. Emerg Infect Dis 2009;15:469-71.
Corman VM, Rasche A, Baronti C, Aldabbagh S, Cadar D, Reusken CB, et al
. Assay optimization for molecular detection of Zika virus. Bulletin of the World Health Org 2016;94:880-92.
Hsih WH, Cheng MY, Ho MW, Chou CH, Lin PC, Chi CY, et al
. Featuring COVID-19 cases via screening symptomatic patients with epidemiologic link during flu season in a medical center of central Taiwan. J Microbiol Immunol Infect 2020;53:459-466.
Peiris JS, Yuen KY, Osterhaus AD, Stöhr K. The severe acute respiratory syndrome. N Engl J Med 2003;349:2431-41.
Ding Y, He L, Zhang Q, Huang Z, Che X, Hou J, et al
. Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: Implications for pathogenesis and virus transmission pathways. J Pathol 2004;203:622-30.
Hong HL, Kim SH, Choi DL, Kwon HH. A case of coronavirus disease 2019-infected liver transplant donor. Am J Transplant 2020;20:2938-41.
Modjarrad K. Treatment strategies for Middle East respiratory syndrome coronavirus. J Virus Erad 2016;2:1-4.
Behzadi MA, Leyva-Grado VH. Overview of current therapeutics and novel candidates against influenza, respiratory syncytial virus, and Middle East respiratory syndrome coronavirus infections. Front Microbiol 2019;10:1327.
Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. The cytokine release syndrome (CRS) of severe COVID-19 and Interleukin-6 receptor (IL-6R) antagonist Tocilizumab may be the key to reduce the mortality. Int J Antimicrob Agents 2020; Mar 29:105954.
Al-Tawfiq JA, Momattin H, Dib J, Memish ZA. Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: An observational study. Int J Infect Dis 2014;20:42-6.
Al-Tawfiq JA, Memish ZA. Update on therapeutic options for Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Expert Rev Anti Infect Ther 2017;15:269-75.
Rabaan AA, Alahmed SH, Bazzi AM, Alhani HM. A review of candidate therapies for Middle East respiratory syndrome from a molecular perspective. J Med Microbiol 2017;66:1261-74.
Rabaan AA. Middle East respiratory syndrome coronavirus: Five years later. Expert Rev Respir Med 2017;11:901-12.
Soltani S, Zakeri AM, Karimi MR, Rezayat SA, Anbaji FZ, Tabibzadeh A, et al
. A systematic literature review of current therapeutic approaches for COVID-19 patients. J Pharm Res Int 2020; May 18:13-25.