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European Journal of Medical Research
Published in: European Journal of Medical Research 1/2021

Open Access 01-12-2021 | SARS-CoV-2 | Review

Characterization of SARS-CoV-2 different variants and related morbidity and mortality: a systematic review

Authors: SeyedAhmad SeyedAlinaghi, Pegah Mirzapour, Omid Dadras, Zahra Pashaei, Amirali Karimi, Mehrzad MohsseniPour, Mahdi Soleymanzadeh, Alireza Barzegary, Amir Masoud Afsahi, Farzin Vahedi, Ahmadreza Shamsabadi, Farzane Behnezhad, Solmaz Saeidi, Esmaeil Mehraeen, Shayesteh Jahanfar

Published in: European Journal of Medical Research | Issue 1/2021

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Abstract

Introduction

Coronavirus Disease-2019 (SARS-CoV-2) started its devastating trajectory into a global pandemic in Wuhan, China, in December 2019. Ever since, several variants of SARS-CoV-2 have been identified. In the present review, we aimed to characterize the different variants of SARS-CoV-2 and explore the related morbidity and mortality.

Methods

A systematic review including the current evidence related to different variants of SARS-CoV-2 and the related morbidity and mortality was conducted through a systematic search utilizing the keywords in the online databases including Scopus, PubMed, Web of Science, and Science Direct; we retrieved all related papers and reports published in English from December 2019 to September 2020.

Results

A review of identified articles has shown three main genomic variants, including type A, type B, and type C. we also identified three clades including S, V, and G. Studies have demonstrated that the C14408T and A23403G alterations in the Nsp12 and S proteins are the most prominent alterations in the world, leading to life-threatening mutations.The spike D614G amino acid change has become the most common variant since December 2019. From missense mutations found from Gujarat SARS-CoV-2 genomes, C28854T, deleterious mutation in the nucleocapsid (N) gene was significantly associated with patients' mortality. The other significant deleterious variant (G25563T) is found in patients located in Orf3a and has a potential role in viral pathogenesis.

Conclusion

Overall, researchers identified several SARS-CoV-2 variants changing clinical manifestations and increasing the transmissibility, morbidity, and mortality of COVID-19. This should be considered in current practice and interventions to combat the pandemic and prevent related morbidity and mortality.
Literature
1.
2.
3.
De Vito A, Fiore V, Princic E, Geremia N, Panu Napodano CM, Muredda AA, et al. Predictors of infection, symptoms development, and mortality in people with SARS-CoV-2 living in retirement nursing homes. PLoS ONE. 2021;16(3):e0248009-e.PubMedPubMedCentralCrossRef
4.
De Vito A, Fau GN, Fiore V, Fau FV, Princic E, Fau PE, Babudieri S, Fau BS, Madeddu G, Madeddu G. Clinical features, laboratory findings and predictors of death in hospitalized patients with COVID-19 in Sardinia Italy. Eur Rev Med Pharmacol Sci. 2020;24(14):7861–8.PubMed
5.
Vaira LA-OX, Deiana G, Fois AG, Pirina P, Madeddu G, De Vito A, et al. Objective evaluation of anosmia and ageusia in COVID-19 patients: single–center experience on 72 cases. Head neack. 2020;42:1252–8.CrossRef
6.
Zinellu A, Arru F, De Vito A, Sassu A, Valdes G, Scano V, et al. The De Ritis ratio as prognostic biomarker of in-hospital mortality in COVID-19 patients. Eur J Clin Invest. 2021;51(1):13427.CrossRef
7.
SeyedAlinaghi S, Ghadimi M, Hajiabdolbaghi M, Rasoolinejad M, Abbasian L, Nezhad MH, et al. Prevalence of COVID-19-like symptoms among people living with HIV, and using antiretroviral therapy for prevention and treatment. Curr HIV Res. 2020;18:373–80.PubMed
8.
Jary A, Leducq V, Malet I, Marot S, Klement-Frutos E, Teyssou E, et al. Evolution of viral quasispecies during SARS-CoV-2 infection. Clin Microbiol Infect. 2020;26(11):1560-e1.PubMedPubMedCentralCrossRef
9.
Álvarez-Díaz DA, Franco-Muñoz C, Laiton-Donato K, Usme-Ciro JA, Franco-Sierra ND, Flórez-Sánchez AC, et al. Molecular analysis of several in-house rRT-PCR protocols for SARS-CoV-2 detection in the context of genetic variability of the virus in Colombia. Infect Genet Evolut. 2020;84:104390.CrossRef
10.
Lokman SM, Rasheduzzaman M, Salauddin A, Barua R, Tanzina AY, Rumi MH, et al. Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: a computational biology approach. Infect Genet Evolut. 2020;84:104389.CrossRef
11.
Korber B, Fischer WM, Gnanakaran S, Yoon H, Theiler J, Abfalterer W, et al. Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus. Cell. 2020;182:812–27.PubMedPubMedCentralCrossRef
12.
Wu F, Zhao S, Yu B, Chen Y-M, Wang W, Song Z-G, et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020;579(7798):265–9.PubMedPubMedCentralCrossRef
13.
14.
Gong Y-N, Tsao K-C, Hsiao M-J, Huang C-G, Huang P-N, Huang P-W, et al. SARS-CoV-2 genomic surveillance in Taiwan revealed novel ORF8-deletion mutant and clade possibly associated with infections in middle East. Emerg Microb Infect. 2020;9(1):1457–66.CrossRef
15.
Consortium CSME. Molecular evolution of the SARS coronavirus during the course of the SARS epidemic in China. Science. 2004;303(5664):1666–9.CrossRef
16.
17.
Muth D, Corman VM, Roth H, Binger T, Dijkman R, Gottula LT, et al. Attenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission. Sci Rep. 2018;8(1):1–1.CrossRef
18.
Zhang L, Yang J-R, Zhang Z, Lin Z. Genomic variations of SARS-CoV-2 suggest multiple outbreak sources of transmission. medRxiv. 2020;7:154.
19.
Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020;583(7816):459–68.PubMedPubMedCentralCrossRef
20.
Bhowmik D, Pal S, Lahiri A, Talukdar A, Paul S. Emergence of multiple variants of SARS-CoV-2 with signature structural changes. bioRxiv. 2020;91:157.
21.
Alouane T, Laamarti M, Essabbar A, Hakmi M, Bouricha EM, Chemao-Elfihri M, et al. Genomic diversity and hotspot mutations in 30,983 SARS-CoV-2 genomes: moving toward a universal vaccine for the “confined virus”? Pathogens. 2020;9(10):829.PubMedCentralCrossRef
22.
Al-Tawfiq JA, Leonardi R, Fasoli G, Rigamonti D. Prevalence and fatality rates of COVID-19: what are the reasons for the wide variations worldwide? Travel Med Infect Dis. 2020;35:101711.PubMedPubMedCentralCrossRef
23.
Armengaud J, Delaunay-Moisan A, Thuret JY, Van Anken E, Acosta-Alvear D, Aragón T, et al. The importance of naturally attenuated Sars-Cov-2 in the fight against Covid-19. Environ Microbiol. 2020;22(6):1997–2000.PubMedCrossRef
24.
Bajaj A, Purohit HJ. Understanding SARS-CoV-2: genetic diversity, transmission and cure in human. Indian J Microbiol. 2020;160:398–401.CrossRef
25.
Laha S, Chakraborty J, Das S, Manna SK, Biswas S, Chatterjee R. Characterizations of SARS-CoV-2 mutational profile, spike protein stability and viral transmission. Infect Genet Evolut. 2020;85:104445.CrossRef
26.
27.
Blackstone NW, Blackstone SR, Berg AT. Variation and multilevel selection of SARS-CoV-2. Evolution. 2020;74:2429–34.PubMedCrossRef
28.
Canhui C, Huang L, Liu K, Ma K, Tian Y, Qin Y, et al. Amino acid variation analysis of surface spike glycoprotein at 614 in SARS-CoV-2 strains. Genes Dis. 2020;7:567–77.CrossRef
29.
Castillo AE, Parra B, Tapia P, Acevedo A, Lagos J, Andrade W, et al. Phylogenetic analysis of the first four SARS-CoV-2 cases in Chile. J Med virol. 2020;92:1562–6.PubMedCrossRef
30.
31.
Forni D, Cagliani R, Pontremoli C, Mozzi A, Pozzoli U, Clerici M, et al. Antigenic variation of SARS-CoV-2 in response to immune pressure. Mol Ecol. 2020;9:7861.
32.
33.
Gómez-Carballa A, Bello X, Pardo-Seco J, Martinón-Torres F, Salas A. Mapping genome variation of SARS-CoV-2 worldwide highlights the impact of COVID-19 super-spreaders. Genome Res. 2020;30(10):1434–48.PubMedPubMedCentralCrossRef
34.
35.
Graudenzi A, Maspero D, Angaroni F, Piazza R, Ramazzotti D. Mutational signatures and heterogeneous host response revealed via large-scale characterization of SARS-CoV-2 genomic diversity. bioRxiv. 2020;110:375.
36.
Islam OK, Al-Emran HM, Hasan MS, Anwar A, Jahid MIK, Hossain MA. Emergence of European and north American mutant variants of SARS-CoV-2 in South–East Asia. Transbound Emerg Dis. 2020;68:824–32.PubMedCrossRef
37.
Jain A, Rophina M, Mahajan S, Krishnan BB, Sharma M, Mandal S, et al. Analysis of the potential impact of genomic variants in SARS-CoV-2 genomes from India on molecular diagnostic assays. bioRxiv. 2020;7:200636.
38.
Joshi M, Puvar A, Kumar D, Ansari A, Pandya M, Raval J, et al. Genomic variations in SARS-CoV-2 genomes from Gujarat: underlying role of variants in disease epidemiology. bioRxiv. 2020;555:549.
39.
Junejo Y, Ozaslan M, Safdar M, Khailany RA, Rehman S, Yousaf W, et al. Novel SARS-CoV-2/COVID-19: origin, pathogenesis, genes and genetic variations, immune responses and phylogenetic analysis. Gene Rep. 2020;20:100752.PubMedPubMedCentralCrossRef
40.
Kouriba B, Dürr A, Rehn A, Sangaré AK, Traoré BY, Bestehorn-Willmann MS, et al. First phylogenetic analysis of Malian SARS-coV-2 sequences provides molecular insights into the genomic diversity of the Sahel region. Viruses. 2020;12(11):1251.PubMedCentralCrossRef
41.
42.
Kozlovskaya 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.PubMedPubMedCentralCrossRef
43.
Latini A, Agolini E, Novelli A, Borgiani P, Giannini R, Gravina P, et al. COVID-19 and genetic variants of protein involved in the SARS-CoV-2 entry into the host cells. Genes. 2020;11(9):1010.PubMedCentralCrossRef
44.
Lau S-Y, Wang P, Mok BW-Y, Zhang AJ, Chu H, Lee AC-Y, et al. Attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction. Emerg Microb Infect. 2020;9(1):837–42.CrossRef
45.
Lee JW, Lee IH, Sato T, Kong SW, Iimura T. Genetic variation analyses indicate conserved SARS-CoV-2-host interaction and varied genetic adaptation in immune-response factors in modern human evolution. Dev Growth Differ. 2021;63:219–27.PubMedPubMedCentralCrossRef
46.
Liu S, Shen J, Fang S, Li K, Liu J, Yang L, et al. Genetic spectrum and distinct evolution patterns of SARS-CoV-2. medRxiv. 2020;5:536.
47.
Lokman SM, Rasheduzzaman M, Salauddin A, Barua R, Tanzina AY, Rumi MH, et al. Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein a computational biology approach. Infect Genet Evol. 2020;84:104389.PubMedPubMedCentralCrossRef
48.
Muhammad Ansori AN, Dhea Kharisma V, Sabilil Muttaqin S, Antonius Y, Parikesit AA. Genetic variant of SARS-CoV-2 isolates in Indonesia: spike glycoprotein gene. J Pure Appl Microbiol. 2020;14(1):971–8.CrossRef
49.
Mukherjee M, Goswami S. Global cataloguing of variations in untranslated regions of viral genome and prediction of key host RNA binding protein-microRNA interactions modulating genome stability in SARS-CoV-2. PLoS ONE. 2020;15(8):e0237559.PubMedPubMedCentralCrossRef
50.
Pachetti M, Marini B, Benedetti F, Giudici F, Mauro E, Storici P, et al. Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant. J Transl Med. 2020;18:1–9.CrossRef
51.
52.
Pardo-Seco J, Gómez-Carballa A, Bello X, Martinón-Torres F, Salas A. Pitfalls of barcodes in the study of worldwide SARS-CoV-2 variation and phylodynamics. Zool Res. 2021;42(1):87.PubMedPubMedCentralCrossRef
53.
Parlikar A, Kalia K, Sinha S, Patnaik S, Sharma N, Vemuri SG, et al. Understanding genomic diversity, pan-genome, and evolution of SARS-CoV-2. Peer J. 2020;8:e9576.PubMedCrossRefPubMedCentral
54.
Peñarrubia 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.PubMedPubMedCentralCrossRef
55.
Peñarrubia L, Ruiz M, Porco R, Rao SN, Vella SA, Juanola-Falgarona M, et al. In response to: multiple assays in a real-time RT-PCR severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) panel can mitigate the risk of loss of sensitivity by new genomic variants during the COVID-19 outbreak. Intern J Infect Dis. 2021;105(241):2.
56.
Portelli S, Olshansky M, Rodrigues CHM, D’Souza EN, Myung Y, Silk M, et al. Exploring the structural distribution of genetic variation in SARS-CoV-2 with the COVID-3D online resource. Nat Genet. 2020;52:999–1001.PubMedCrossRef
57.
Poterico JA, Mestanza O. Genetic variants and source of introduction of SARS-CoV-2 in South America. J Med Virol. 2020;10:2139–45.CrossRef
58.
Romero PE. Comment on “Genetic variants and source of introduction of SARS-CoV-2 in South America.” J Med Virol. 2020;93:28–9.PubMedCrossRef
59.
Sapoval N, Mahmoud M, Jochum M, Liu Y, Elworth RL, Wang Q, et al. Hidden genomic diversity of SARS-CoV-2: implications for qRT-PCR diagnostics and transmission. Genome Res. 2021;31:635–44.PubMedPubMedCentralCrossRef
60.
Sarkar R, Mitra S, Chandra P, Saha P, Banerjee A, Dutta S, et al. Comprehensive analysis of genomic diversity of SARS-CoV-2 in different geographic regions of India: an endeavour to classify Indian SARS-CoV-2 strains on the basis of co-existing mutations. Adv Virol. 2021;166(3):801–12.
61.
Shen Z, Xiao Y, Kang L, Ma W, Shi L, Zhang L, et al. Genomic diversity of severe acute respiratory syndrome-coronavirus 2 in patients with coronavirus disease. Clin Infect Dis. 2020;4:536.
62.
Singh PK, Kulsum U, Rufai SB, Mudliar SR, Singh S. Mutations in SARS-CoV-2 leading to antigenic variations in spike protein: a challenge in vaccine development. J Lab Phys. 2020;12(2):154–60.
63.
64.
Thielen PM, Wohl S, Mehoke T, Ramakrishnan S, Kirsche M, Falade-Nwulia O, et al. Genomic diversity of SARS-CoV-2 during early introduction into the united states national capital region. MedRxiv. 2020;181:997.
65.
Toyoshima 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;65:1075–82.PubMedPubMedCentralCrossRef
66.
Ugurel OM, Ata O, Turgut-Balik D. An updated analysis of variations in SARS-CoV-2 genome. Turkish J Biol Turk Biyoloji Dergisi. 2020;44(3):157–67.CrossRef
67.
van Dorp L, Acman M, Richard D, Shaw LP, Ford CE, Ormond L, et al. Emergence of genomic diversity and recurrent mutations in SARS-CoV-2. Infect Genet Evol. 2020;83:104351.PubMedPubMedCentralCrossRef
68.
Wang C, Liu Z, Chen Z, Huang X, Xu M, He T, et al. The establishment of reference sequence for SARS-CoV-2 and variation analysis. J Med Virol. 2020;92(6):667–74.PubMedCrossRef
69.
Xiao M, Liu X, Ji J, Li M, Li J, Yang L, et al. Multiple approaches for massively parallel sequencing of SARS-CoV-2 genomes directly from clinical samples. Genome Med. 2020;12(1):1–15.CrossRef
70.
Yap PSX, Tan TS, Chan YF, Tee KK, Kamarulzaman A, Teh CSJ. An Overview of the Genetic Variations of the SARS-CoV-2 genomes isolated in Southeast Asian countries. J Microbiol Biotechnol. 2020;30(7):962–6.PubMedCrossRef
71.
Zhu Z, Liu G, Meng K, Yang L, Liu D, Meng G. Rapid spread of mutant alleles in worldwide SARS-CoV-2 strains revealed by genome-wide single nucleotide polymorphism and variation analysis. Genome Biol Evol. 2021;13(2):15.CrossRef
72.
Novazzi F, Genoni A, Spezia PG, Focosi D, Zago C, Colombo A, et al. Introduction of SARS-CoV-2 variant of concern 20h/501Y. V2 (B. 1.351) from Malawi to Italy. Emerg Microb Infect. 2021;10(1):710–2.CrossRef
73.
Faria NR, Mellan TA, Whittaker C, Claro IM, Candido DdS, Mishra S, et al. Genomics and epidemiology of the P. 1 SARS-CoV-2 lineage in Manaus Brazil. Science. 2021;372:815–21.PubMedPubMedCentralCrossRef
74.
Ferreira I, Datir R, Papa G, Kemp S, Meng B, Rakshit P, et al. SARS-CoV-2 B 1617 emergence and sensitivity to vaccine-elicited antibodies. bioRxiv. 2021;35:108950.
75.
Ovsyannikova IG, Haralambieva IH, Crooke SN, Poland GA, Kennedy RB. The role of host genetics in the immune response to SARS-CoV-2 and COVID-19 susceptibility and severity. Immunol Rev. 2020;296(1):205–19.PubMedPubMedCentralCrossRef
76.
77.
Narasimhan VM, Rahbari R, Scally A, Wuster A, Mason D, Xue Y, et al. Estimating the human mutation rate from autozygous segments reveals population differences in human mutational processes. Nat Commun. 2017;8(1):1–7.CrossRef
78.
79.
80.
81.
Cao Y, Li L, Feng Z, Wan S, Huang P, Sun X, et al. Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations. Cell Discov. 2020;6(1):1–4.CrossRef
82.
Korber B, Fischer WM, Gnanakaran S, Yoon H, Theiler J, Abfalterer W, et al. Tracking changes in SARS-CoV-2 spike: evidence that D614G increases infectivity of the COVID-19 virus. Cell. 2020;182(4):812-27.e19.PubMedPubMedCentralCrossRef
83.
Chan JF-W, Yuan S, Kok K-H, To KK-W, Chu H, Yang J, et al. A familial cluster of pneumonia associated with the novel coronavirus indicating person to person transmission a study of a family cluster. Lancet. 2020;395(10223):514–23.PubMedPubMedCentralCrossRef
84.
85.
Velavan TP, Meyer CG. The COVID-19 epidemic. Trop Med Intern Health. 2020;25(3):278.CrossRef
86.
87.
Bermejo-Martin JF, Almansa R, Menéndez R, Mendez R, Kelvin DJ, Torres A. Lymphopenic community acquired pneumonia as signature of severe COVID-19 infection. J Infect. 2020;80(5):e23.PubMedPubMedCentralCrossRef
88.
Anderson RM, Heesterbeek H, Klinkenberg D, Hollingsworth TDJTL. How will country-based mitigation measures influence the course of the COVID-19 epidemic? Lancet. 2020;395(10228):931–4.PubMedPubMedCentralCrossRef
89.
90.
Kang S-J, Jung SI. Age-related morbidity and mortality among patients with COVID-19. Infect Chemothe. 2020;52(2):154.CrossRef
91.
Promislow DE. A geroscience perspective on COVID-19 mortality. J Gerontol Ser A. 2020;75(9):e30-3.CrossRef
Metadata
Title
Characterization of SARS-CoV-2 different variants and related morbidity and mortality: a systematic review
Authors
SeyedAhmad SeyedAlinaghi
Pegah Mirzapour
Omid Dadras
Zahra Pashaei
Amirali Karimi
Mehrzad MohsseniPour
Mahdi Soleymanzadeh
Alireza Barzegary
Amir Masoud Afsahi
Farzin Vahedi
Ahmadreza Shamsabadi
Farzane Behnezhad
Solmaz Saeidi
Esmaeil Mehraeen
Shayesteh Jahanfar
Publication date
01-12-2021
Publisher
BioMed Central
Published in
European Journal of Medical Research / Issue 1/2021
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-021-00524-8

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