Journal of Medical Society

REVIEW ARTICLE
Year
: 2020  |  Volume : 34  |  Issue : 1  |  Page : 1--3

SARS-CoV-2 variant: Its clinical importance and molecular epidemiology


Viroj Wiwanitkit 
 Department of Community Medicine, Dr. DY Patil University, Pune, Maharashtra, India; Department of Tropical Medicine, Hainan Medical University, Haikou, China; Department of Biological Science, Joseph Ayo Babalola University, Ikeji-Arakeji, Nigeria; Department of Medical Science, Faculty of Medicine, University of Nis, Nis, Serbia

Correspondence Address:
Viroj Wiwanitkit
Dr. DY Patil University, Pune, Maharashtra; Hainan Medical University, Haikou; Joseph Ayo Babalola University, Ikeji-Arakeji; Faculty of Medicine, University of Nis, Nis

Abstract

Coronavirus disease 2019 (COVID-19) is a newly emerging disease. COVID-19 pandemic becomes a global problem in 2020. The disease causes more than 22 infected persons worldwide. Since this respiratory infection is a new coronavirus infection, the knowledge of its clinical epidemiology is very important for proper management. The diagnosis of the infection is usually based on molecular diagnosis. The molecular study of the pathogenic virus, SARS-CoV-2, might detect a mutated virus. The COVID-19 with mutated virus is an interesting emerging problem in medicine. There are some new reported on SARS-CoV-2 variants that are associated with altered clinical feature. In this short review article, the author summarizes and discusses the data on SARS-CoV-2 variant. The clinical importance and molecular epidemiology of SARS-CoV-2 variant are focused on the present article.



How to cite this article:
Wiwanitkit V. SARS-CoV-2 variant: Its clinical importance and molecular epidemiology.J Med Soc 2020;34:1-3


How to cite this URL:
Wiwanitkit V. SARS-CoV-2 variant: Its clinical importance and molecular epidemiology. J Med Soc [serial online] 2020 [cited 2020 Nov 24 ];34:1-3
Available from: https://www.jmedsoc.org/text.asp?2020/34/1/1/300554


Full Text



 Introduction



Coronavirus disease 2019 (COVID-19) is a new emerging infection caused by a novel coronavirus, SARS-CoV-2. This new infection was firstly reported from Wuhan, China, in 2019. COVID-19 already spreads worldwide causing a pandemic. At present, COVID-19 is already a global public health problem. At present, more than 22 million people throughout the world (https://www.worldometers.info/coronavirus/, data at August 19, 2020) already have infections. Typically, this infection is transmitted from humans to humans through respiratory contact. COVID-19 can cause many clinical problems and death. Although several efforts are being made to control this emerging infectious disease globally, it is still not successful in global disease containment.

The disease can spread from a patient to others through respiratory contact.[1],[2] There is also a possibility that the disease might be transmitted through atypical modes of transmission.[3] At present, a rapid disease spreading still occurs worldwide. Since this respiratory infection is a new coronavirus infection, medical and public health practitioner still requires update knowledge of the disease. Of several data, the knowledge of its clinical epidemiology is very important for proper public health management.[4] In general, the diagnosis of the infection is usually based on molecular diagnostic test.[5],[6] The molecular study of the pathogenic virus, SARS-CoV-2, might sometimes identify a mutated virus. The COVID-19 with mutated virus is an interesting phenomenon. The variant might cause a superimposed emerging problem to typical COVID-19. There are some new reports on SARS-CoV-2 variants. Some reports present the association between molecular genetic variation and clinical feature of the infection. In this short review article, the author summarizes and discusses the data on SARS-CoV-2 variant. The clinical importance and molecular epidemiology of SARS-CoV-2 variant are focused in the present article.

 Molecular Epidemiology and Sars-Cov-2



The molecular epidemiology is a specific epidemiological approach based on molecular diagnostic finding. The molecular epidemiology can give a genetic proof, not phenotypic proof, a disease. During an outbreak, there might be many patients having the same disease, but the underlying causative pathogen might be different. The specific focus on molecular structure of the pathogen can give further data for implication on clinical interrelationship.[6]

Basically, the genetic data of a pathogen might be revealed by a molecular diagnosis. The data of identified pathogen from different cases can be further analyzed. The novel bioinformatic tool might play a role in this process. At first, a comparative genomics might be applied for comparative alignment study among sequences of pathogen from different infected cases. This can result in data on similarity of the pathogen.[4],[7] If there is no difference, it might imply that the disease has a genetic stability and there should be not atypical clinical problem due to genetic alteration. Nevertheless, there is already a genetic alteration of SARS-CoV-2. The SARS-CoV-2 variant already occurs, and it might further result in new clinical problem.

Additional to a standard comparative genomics analysis, a phylogenomic analysis is also applicable for analysis of the data on sequences of pathogen from different infected cases. The phylogenetic pattern from a phylogenetic tree might be constructed and can reflect the evolution of the pathogen. This pattern might be interpreted in time and place dimensions. For example, it can help give draft information that a pathogen detected in a setting should be transmitted from which origin.[4],[7] This approach gives better scientific evidence than a simple classic epidemiological approach that has a low reliability.[2]

There are many advantages of molecular epidemiology study on SARS-CoV-2. First, it can give reliable evidence on confirmed incidence of COVID-19. Next, it can help trace the dynamicity of disease transmission. The spreading pattern of COVID-19 from a place to another place and from a person to another person can be clarified by molecular epidemiology data. Finally, the molecular epidemiology surveillance can help get an early sign of a possible genetic drift that might cause a new atypical COVID-19 problem.[8] In the future, when a specific drug against COVID-19 is successfully developed, the monitoring of mutated virus can give an early sign of possible resistance and it can help predict the trend of disease spreading and response of antiviral medication. Finally, a similar application to the follow-up of vaccination is possible. At present, there are some licensed vaccines, such as Chinese and Russian vaccines, and the monitoring of mutated variant can give data on a possible vaccine escape variant. If a new variant with possibility of drug resistance or vaccine escape is identified, an early warning can be given and urgent finding for new drug and vaccine will be promptly done.[9]

It should note that the occurrence of SARS-CoV-2 variant is already confirmed. As earlier mentioned, it is possible that there is a mutation of the SARS-CoV-2 pathogen. There are many reports on new mutations. Focusing on mutated SARS-CoV-2 pathogen, there are already some reports on this specific issue. Laamarti et al. reported the observation from molecular virology laboratory that there are at least six different strains of SARS-CoV-2.[10] The summarization of important reports on SARS-CoV-2 variant from different geographical locations is given in [Table 1]. The nature of data from different regions might be different.[11],[12],[13],[14],[15],[16],[17] In addition, in some areas, there might be no or extremely few data. This is usually due to the local policies to block the data generalization or the lack of molecular diagnostic laboratory or lack of expert who can summarize and publish the data internationally.{Table 1}

 Clinical Importance of Sars-Cov-2 Variant



Due to the high spreading rate of the new virus within a short period of time, there are many millions of infected patients. For each transmission of disease, the virus might pass the replication process during transmission. The mutation is a possible phenomenon that can naturally occur. In fact, the typical SARS-CoV-2 virus is believed to be a cross-species coronavirus from animals. Although the exact origin of the virus is not known, it is believed that there was a sense mutation of an animal coronavirus that results in a cross-species transmission to humans and caused a new emerging human disease. The possible clinical significant problems due to SARS-CoV-2 variant are hereby presented.

Problem in diagnosis

The molecular structure change of the SARS-CoV-2 can cause the problem of diagnosis. The polymerase chain reaction (PCR) tool might give a false negative result in case that there is a mutation. It is a common pitfall in disease control in many countries. There is a confirmed problem on the diagnosis of a disease in a setting although it was recently not detectable in another setting.[18] The use of new PCR tool that focuses on many diagnostic molecular targets of the pathogen might be a solution to solve the problem.[19]

Change of virus infectivity

Some mutations can cause a significant change of the pathogen and promote infectivity.[20],[21] Regarding the pathogenesis explanation, the nutation primarily causes a structural change of the virus, and this can further affect the binding process between virus and pathogen receptor.[22] Some mutations might result in a lowering of required binding energy, and this means an easier infection process.[22]

Change of virus antigenicity

Some mutations can cause a significant change of molecular structure and further alter the antigenicity of the pathogen.[20] The mutation change causes structural change and can further alter the antigenic property.[23],[24] The change of epitope function can result in a new vaccine escape strain.[24] This can lead to the problem in response to the vaccine, and this is an important consideration in clinical vaccinology.[23]

 Conclusion



Atypical variant SARS-CoV-2 virus already occurs and might become a newly emerging problem superimposed to the pandemic COVID-19. The molecular mutation in SARS-CoV-2 can result in variant, and if there is a significant genetic change, it might result in a COVID-19 with new clinical feature. At present, there are already some reports on SARS-CoV-2 variant, and a relationship with some clinical problems, such as infectivity and immunological response, is already mentioned. Since the standard diagnosis of COVID-19 is still based on molecular diagnostic test, the clinical surveillance on molecular epidemiology of SARS-CoV-2 variant is possible and should be performed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Jayaweera M, Perera H, Gunawardana B, Manatunge J. Transmission of COVID-19 virus by droplets and aerosols: A critical review on the unresolved dichotomy. Environ Res 2020;188:109819.
2Wiwanitkit V. COVID-19: Talk of epidemiological issue – Places, presentation and transmission-Vedeo presentation. Adv Trop Med Pub Health Int 2020;10:19.
3Wiwanitkit V. Atypical modes of COVID-19 transmission: how likely are they? Wiwanitkit V. Epidemiol Health. 2020;42:e2020059.
4Parczewski M, Ciechanowicz A. Molecular epidemiology of SARS CoV-2: A review of current data on genetic variability of the virus. Pol Arch Intern Med. 2020 Aug 11. doi: 10.20452/pamw.15550. Online ahead of print.
5Mungmungpuntipantip R, Wiwanitkit V. RT-PCR tests for COVID-19: Observation on use and cost. Clin Lab. 2020;66. doi: 10.7754/Clin. Lab.2020.200461.
6Shey M, Okeibunor JC, Yahaya AA, Herring BL, Tomori O, Coulibaly SO, et al. Genome sequencing and the diagnosis of novel coronavirus (SARS-COV-2) in Africa: How far are we? Pan Afr Med J 2020;36:80.
7Jamwal S, Gautam A, Elsworth J, Kumar M, Chawla R, Kumar P. An updated insight into the molecular pathogenesis, secondary complications and potential therapeutics of COVID-19 pandemic. Life Sci 2020;257:118105.
8Zuckerman NS, Pando R, Bucris E, Drori Y, Lustig Y, Erster O, et al. Comprehensive analyses of SARS-CoV-2 transmission in a public health virology laboratory. Viruses. 2020;12:854.
9Danchin A, Timmis K. SARS-CoV-2 variants: Relevance for symptom granularity, epidemiology, immunity (herd, vaccines), virus origin and containment? Environ Microbiol 2020;22:2001-6.
10Laamarti M, Chemao-Elfihri MW, Kartti S, Laamarti R, Allam L, Ouadghiri M, et al. Genome sequences of six SARS-CoV-2 strains isolated in morocco, obtained using oxford nanopore minion technology. Microbiol Resour Announc. 2020;9:e00767-20.
11Lai A, Bergna A, Caucci S, Clementi N, Vicenti I, Dragoni F, et al. Molecular tracing of SARS-CoV-2 in Italy in the first three months of the epidemic. Viruses. 2020;12:798.
12Licastro D, Rajasekharan S, Dal Monego S, Segat L, D'Agaro P, Marcello A. Isolation and full-length genome characterization of SARS-CoV-2 from COVID-19 Cases in Northern Italy. J Virol. 2020;94:e00543-20.
13Kozlovskaya L, Piniaeva A, Ignatyev G, Selivanov A, Shishova A, Kovpak A, et al. Isolation and phylogenetic analysis of SARS-CoV-2 variants collected in Russia during the COVID-19 outbreak. Int J Infect Dis 2020;99:40-6.
14Jin X, Xu K, Jiang P, Lian J, Hao S, Yao H, et al. Virus strain from a mild COVID-19 patient in Hangzhou represents a new trend in SARS-CoV-2 evolution potentially related to Furin cleavage site. Emerg Microbes Infect 2020;9:1474-88.
15Kim SJ, Nguyen VG, Park YH, Park BK, Chung HC. A novel synonymous mutation of SARS-CoV-2: Is this possible to affect their antigenicity and immunogenicity? Vaccines (Basel). 2020;8:220.
16Toyoshima Y, Nemoto K, Matsumoto S, Nakamura Y, Kiyotani K. SARS-CoV-2 genomic variations associated with mortality rate of COVID-19. J Hum Genet. 2020 Jul 22:1-8. doi: 10.1038/s10038-020-0808-9. Online ahead of print.
17Kaushal N, Gupta Y, Goyal M, Khaiboullina SF, Baranwal M, Verma SC. Mutational frequencies of SARS-CoV-2 genome during the beginning months of the outbreak in USA. Pathogens. 2020;9:565.
18Sriwijitalai W, Wiwnaitkit V. Estimated rate of neglected COVID-19 reporting according to legal surveillance system implication on problem of disease control. Int J Prev Med 2020;11:105
19Peñarrubia L, Ruiz M, Porco R, Rao SN, Juanola-Falgarona M, Manissero D, et al. Multiple assays in a real-time RT-PCR SARS-CoV-2 panel can mitigate the risk of loss of sensitivity by new genomic variants during the COVID-19 outbreak. Int J Infect Dis 2020;97:225-9.
20Li Q, Wu J, Nie J, Zhang L, Hao H, Liu S, et al. The impact of mutations in SARS-CoV-2 spike on viral infectivity and antigenicity. Cell 2020;182:1284-94000000000.
21Chen J, Wang R, Wang M, Wei GW. Mutations strengthened SARS-CoV-2 infectivity. J Mol Biol. 2020 Sep 4;432:5212-26.
22Zou J, Yin J, Fang L, Yang M, Wang T, Wu W, et al. Computational prediction of mutational effects on the SARS-CoV-2 binding by relative free energy calculations. J Chem Inf Model. 2020 Aug 31:acs.jcim.0c00679. doi: 10.1021/acs.jcim.0c00679. Online ahead of print.
23Rice AM, Morales AC, Ho AT, Mordstein C, Mühlhausen S, Watson S, et al. Evidence for strong mutation bias towards, and selection against, U content in SARS-CoV-2: Implications for vaccine design. Mol Biol Evol. 2020 Jul 20:msaa188. doi: 10.1093/molbev/msaa188. Online ahead of print.
24Robson B. COVID-19 Coronavirus spike protein analysis for synthetic vaccines, a peptidomimetic antagonist, and therapeutic drugs, and analysis of a proposed achilles' heel conserved region to minimize probability of escape mutations and drug resistance. Comput Biol Med 2020;121:103749.