The Delta variant is one of the alarming variants of the SARS-CoV-2 virus that have been immensely detrimental and a significant cause of the prolonged pandemic (B.1.617.2). During the SARS-CoV-2 pandemic from December 2020 to October 2021, the Delta variant showed global dominance, and afterwards, the Omicron variant showed global dominance. Delta shows high infectivity rate which accounted for nearly 70% of the cases after December 2020. This review discusses the additional attributes that make the Delta variant so infectious and transmissible. The study also focuses on the significant mutations, namely the L452R and T478K present on the receptor-binding domain of spike (S)-glycoprotein, which confers specific alterations to the Delta variant. Considerably, we have also highlighted other notable factors such as the immune escape, infectivity and re-infectivity, vaccine escape, Ro number, S-glycoprotein stability, cleavage pattern, and its binding affinity with the host cell receptor protein. We have also emphasized clinical manifestations, symptomatology, morbidity, and mortality for the Delta variant compared with other significant SARS-CoV-2 variants. This review will help the researchers to get an elucidative view of the Delta variant to adopt some practical strategies to minimize the escalating spread of the SARS-CoV-2 Delta variant.

Department of Biotechnology School of Life Science and Biotechnology Adamas University Kolkata West Bengal 700126 India

Department of Zoology Fakir Mohan University Vyasa Vihar Balasore 756020 Odisha India

Institute for Skeletal Aging and Orthopaedic Surgery Hallym University Chuncheon Sacred Heart Hospital Chuncheon si 24252 Gangwon do Republic of Korea

Zobrazit více v PubMed

Abu-Raddad LJ, Chemaitelly H, Yassine HM, et al. Pfizer-BioNTech mRNA BNT162b2 Covid-19 vaccine protection against variants of concern after one versus two doses. J Travel Med. 2021;28:taab083. doi: 10.1093/jtm/taab083. PubMed DOI PMC

Antony P, Vijayan R. Molecular dynamics simulation study of the interaction between human angiotensin converting enzyme 2 and spike protein receptor binding domain of the SARS-CoV-2 B. 1.617 Variant. Biomolecules. 2021;11:1244. doi: 10.3390/biom11081244. PubMed DOI PMC

Shiehzadegan S, Alaghemand N, Fox M, et al. Analysis of the Delta variant B. 1.617. 2 COVID-19. Clin Pract. 2021;11:778–784. doi: 10.3390/clinpract11040093. PubMed DOI PMC

Baral P, Bhattarai N, Hossen ML, et al. Mutation-induced changes in the receptor-binding interface of the SARS-CoV-2 Delta variant B. 1.617. 2 and implications for immune evasion. Biochem Biophys Res Commun. 2021;574:14–19. doi: 10.1016/j.bbrc.2021.08.036. PubMed DOI PMC

Beck DA, Alonso DO, Inoyama D, et al. The intrinsic conformational propensities of the 20 naturally occurring amino acids and reflection of these propensities in proteins. Proc Natl Acad Sci USA. 2008;105:12259–12264. doi: 10.1073/pnas.0706527105. PubMed DOI PMC

Bernal JL, et al. Effectiveness of Covid-19 vaccines against the B. 1.617. 2 (Delta) variant. N Engl J Med. 2021;385:585–594. doi: 10.1056/NEJMoa2108891. PubMed DOI PMC

Bhattacharya M, Sharma AR, Dhama K, et al. Omicron variant (B. 1.1. 529) of SARS-CoV-2: understanding mutations in the genome, S-glycoprotein, and antibody-binding regions. GeroScience. 2022;44:619–637. doi: 10.1007/s11357-022-00532-4. PubMed DOI PMC

Bruxvoort KJ, Sy LS, Qian L, Ackerson BK, et al. Effectiveness of mRNA-1273 against Delta, mu, and other emerging variants of SARS-CoV-2: test negative case-control study. bmj. 2021;375:e068848. doi: 10.1136/bmj-2021-068848. PubMed DOI PMC

Burki TK. Lifting of COVID-19 restrictions in the UK and the Delta variant. Lancet Respir Med. 2021;9:e85. doi: 10.1016/S2213-2600(21)00328-3. PubMed DOI PMC

Campbell F, Archer B, Laurenson-Schafer H, et al. Increased transmissibility and global spread of SARS-CoV-2 variants of concern as at June 2021. Euro Surveill. 2021;26:2100509. doi: 10.2807/1560-7917.ES.2021.26.24.2100509. PubMed DOI PMC

Chakraborty C, Bhattacharya M, Sharma AR. Present variants of concern and variants of interest of severe acute respiratory syndrome coronavirus 2: their significant mutations in S-glycoprotein, infectivity, re-infectivity, immune escape and vaccines activity. Rev Med Virol. 2021;32:e2270. doi: 10.1002/rmv.2270. DOI

Chakraborty C, Sharma A, Sharma G, et al. SARS-CoV-2 causing pneumonia-associated respiratory disorder (COVID-19): diagnostic and proposed therapeutic options. Eur Rev Med Pharmacol Sci. 2020;24:4016–4026. PubMed

Chakraborty C, Sharma AR, Bhattacharya M, et al. The current second wave and COVID-19 vaccination status in India. Brain Behav Immun. 2021;96:1–4. doi: 10.1016/j.bbi.2021.05.018. PubMed DOI PMC

Chakraborty C, Sharma AR, Bhattacharya M, et al. Evolution, mode of transmission, and mutational landscape of newly emerging SARS-CoV-2 variants. Mbio. 2021;12:e01140–e11121. doi: 10.1128/mBio.01140-21. PubMed DOI PMC

Chakraborty C, Sharma AR, Bhattacharya M, et al. Asian-origin approved COVID-19 vaccines and current status of COVID-19 vaccination program in Asia: a critical analysis. Vaccines. 2021;9:600. doi: 10.3390/vaccines9060600. PubMed DOI PMC

Chakraborty C, Sharma AR, Bhattacharya M, et al. Ongoing clinical trials of vaccines to fight against COVID-19 pandemic. Immune Netw. 2021;21:e5. doi: 10.4110/in.2021.21.e5. PubMed DOI PMC

Chakraborty C, Sharma AR, Bhattacharya M, et al. A paradigm shift in the combination changes of SARS-CoV-2 variants and increased spread of Delta variant (B. 1.617. 2) across the world. Aging Dis. 2022;13:927–942. doi: 10.14336/AD.2021.1117. PubMed DOI PMC

Chakraborty C, Sharma AR, Bhattacharya M, et al. Comparative genomics, evolutionary epidemiology, and RBD-hACE2 receptor binding pattern in B. 1.1. 7 (Alpha) and B. 1.617. 2 (Delta) related to their pandemic response in UK and India. Infect Genet Evol. 2022;101:105282. doi: 10.1016/j.meegid.2022.105282. PubMed DOI PMC

Chakraborty C, Bhattacharya M, Sharma AR. Emerging mutations in the SARS-CoV-2 variants and their role in antibody escape to small molecule-based therapeutic resistance. Curr Opin Pharmacol. 2022;62:64–73. doi: 10.1016/j.coph.2021.11.006. PubMed DOI PMC

Chakraborty C, Bhattacharya M, Sharma AR, et al. Recombinant SARS-CoV-2 variants XD, XE, and XF: the emergence of recombinant variants requires an urgent call for research–Correspondence. Int J Surg. 2022;102:106670. doi: 10.1016/j.ijsu.2022.106670. PubMed DOI PMC

Chakraborty C, Sharma AR, Bhattacharya M, et al. A detailed overview of immune escape, antibody escape, partial vaccine escape of SARS-CoV-2 and their emerging variants with escape mutations. Front Immunol. 2022;13:801522. doi: 10.3389/fimmu.2022.801522. PubMed DOI PMC

Chemmama IE, Pelea AC, Bhandari YR, et al. Structural propensities and entropy effects in peptide helix-coil transitions. Phys Rev E. 2012;86:031915. doi: 10.1103/PhysRevE.86.031915. PubMed DOI

Cherian S, Potdar V, Jadhav S, et al. SARS-CoV-2 spike mutations, L452R, E484Q and P681R, in the second wave of COVID-19 in Maharashtra, India. Microorganisms. 2021;9:1542. doi: 10.3390/microorganisms9071542. PubMed DOI PMC

CDC (2021) SARS-CoV-2 variant classifications and definitions. https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-classifications.html (Acession date 12 Nov 2021)

Del Rio C, Malani PN, Omer SB. Confronting the Delta variant of SARS-CoV-2, summer 2021. JAMA. 2021;326:1001–1002. doi: 10.1001/jama.2021.14811. PubMed DOI

Dolzhikova I, Gushchin V, Shcheblyakov D et al (2021) One-shot immunization with Sputnik Light (the first component of Sputnik V vaccine) is effective against SARS-CoV-2 Delta variant: efficacy data on the use of the vaccine in civil circulation in Moscow. medRxiv. 10.1101/2021.10.08.21264715

Duong D. Alpha, Beta, Delta, Gamma: what’s important to know about SARS-CoV-2 variants of concern? CMAJ. 2021;193:E1059–E1060. doi: 10.1503/cmaj.1095949. PubMed DOI PMC

Dyer O. Covid-19: unvaccinated face 11 times risk of death from Delta variant. CDC Data Show BMJ. 2021;2021(374):n2282. PubMed

Ella R, Reddy S, Blackwelder W, et al. Efficacy, safety, and lot-to-lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): interim results of a randomised, double-blind, controlled, phase 3 trial. Lancet. 2021;398:2173–2184. doi: 10.1016/S0140-6736(21)02000-6. PubMed DOI PMC

Elbe S, Buckland-Merrett G. Data, disease and diplomacy: GISAID’s innovative contribution to global health. Glob Chall. 2017;1:33–46. doi: 10.1002/gch2.1018. PubMed DOI PMC

Farinholt T, Doddapaneni H, Qin X, et al. Transmission event of SARS-CoV-2 Delta variant reveals multiple vaccine breakthrough infections. BMC Med. 2021;19:1–6. doi: 10.1186/s12916-021-02103-4. PubMed DOI PMC

Finkelstein MT, Mermelstein AG, Parker Miller E, et al. Structural analysis of neutralizing epitopes of the SARS-CoV-2 spike to guide therapy and vaccine design strategies. Viruses. 2021;13:134. doi: 10.3390/v13010134. PubMed DOI PMC

Gobeil SM, Janowska K, McDowell S, et al. Effect of natural mutations of SARS-CoV-2 on spike structure, conformation and antigenicity. Science. 2021;373(6555):eabi622. doi: 10.1126/science.abi6226. PubMed DOI PMC

Gómez CE, Perdiguero B, Esteban M. Emerging SARS-CoV-2 variants and impact in global vaccination programs against SARS-CoV-2/COVID-19. Vaccines. 2021;9:243. doi: 10.3390/vaccines9030243. PubMed DOI PMC

Hall VG, Ferreira VH, Ku T, Ierullo M, et al. Randomized trial of a third dose of mRNA-1273 vaccine in transplant recipients. N Engl J Med. 2021;385:1244–1246. doi: 10.1056/NEJMc2111462. PubMed DOI PMC

Harder T, Külper-Schiek W, Reda S, et al. Effectiveness of COVID-19 vaccines against SARS-CoV-2 infection with the Delta (B. 1.617. 2) variant: second interim results of a living systematic review and meta-analysis, January 1 to August 25 2021. Euro Surveill. 2021;14(26):2100920. PubMed PMC

Hatmal MM, Alshaer W, Al-Hatamleh MA, et al. Comprehensive structural and molecular comparison of spike proteins of SARS-CoV-2, SARS-CoV and MERS-CoV, and their interactions with ACE2. Cells. 2020;9:2638. doi: 10.3390/cells9122638. PubMed DOI PMC

Kannan SR, Spratt AN, Cohen AR, et al. Evolutionary analysis of the Delta and Delta Plus variants of the SARS-CoV-2 viruses. J Autoimmun. 2021;124:102715. doi: 10.1016/j.jaut.2021.102715. PubMed DOI PMC

Katella K (2021) Things to know about the Delta variant. Yale Medicine News. https://www.yalemedicine.org/news/5-things-to-know-delta-variant-covid (Acessed on 12 Jun 2022)

Katul GG, Mrad A, Bonetti S, et al. Global convergence of COVID-19 basic reproduction number and estimation from early-time SIR dynamics. PLoS ONE. 2020;15:e0239800. doi: 10.1371/journal.pone.0239800. PubMed DOI PMC

Kumar S, Thambiraja TS, Karuppanan K, et al. Omicron and Delta variant of SARS-CoV-2: a comparative computational study of spike protein. J Med Virol. 2022;94:1641–1619. doi: 10.1002/jmv.27526. PubMed DOI

Kunal S, Gupta K, Ish P. COVID-19 variants in India: potential role in second wave and impact on vaccination. Heart Lung. 2021;50:784–787. doi: 10.1016/j.hrtlng.2021.05.008. PubMed DOI PMC

Le Bert N, Tan AT, Kunasegaran K, et al. SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Nature. 2020;584:457–462. doi: 10.1038/s41586-020-2550-z. PubMed DOI

Li XN, Huang Y, Wang W, et al. Effectiveness of inactivated SARS-CoV-2 vaccines against the Delta variant infection in Guangzhou: a test-negative case–control real-world study. Emerg Microbes Infect. 2021;10:1751–1759. doi: 10.1080/22221751.2021.1969291. PubMed DOI PMC

Liu Y, Rocklöv J. The reproductive number of the Delta variant of SARS-CoV-2 is far higher compared to the ancestral SARS-CoV-2 virus. J Travel Med. 2021;28:taab124. doi: 10.1093/jtm/taab124. PubMed DOI PMC

Liu Z, VanBlargan LA, Bloyet LM, et al. Identification of SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization. Cell Host Microbe. 2021;29(477–488):e474. PubMed PMC

McCallum M, Bassi J, De Marco A, et al. SARS-CoV-2 immune evasion by variant B. 1.427/B. 1.429 variant of concern. Science. 2021;373:648–654. doi: 10.1126/science.abi7994. PubMed DOI PMC

Menni C, Valdes AM, Polidori L, et al. Symptom prevalence, duration, and risk of hospital admission in individuals infected with SARS-CoV-2 during periods of Omicron and Delta variant dominance: a prospective observational study from the ZOE COVID Study. Lancet. 2022;399:1618–1624. doi: 10.1016/S0140-6736(22)00327-0. PubMed DOI PMC

Mlcochova P, Kemp S, Dhar MS et al (2021) SARS-CoV-2 B. 1.617. 2 Delta variant emergence and vaccine breakthrough. biorxiv. 10.1101/2021.05.08.443253

Moderbacher CR, Ramirez SI, Dan JM, et al. Antigen-specific adaptive immunity to SARS-CoV-2 in acute COVID-19 and associations with age and disease severity. Cell. 2020;183(996–1012):e1019. PubMed PMC

Mohapatra RK, Tiwari R, Sarangi AK, et al. Twin combination of Omicron and Delta variant triggering a Tsunami wave of ever high surges in COVID-19 cases: a challenging global threat with a special focus on Indian sub-continent. J Med Virol. 2022;94:1761–1765. doi: 10.1002/jmv.27585. PubMed DOI PMC

Nextstrain (2021) Nextstrain SARS-CoV-2 resources, on Nextstrain. https://nextstrain.org/sars-cov-2/ (Acessed on 27 Oct 2021)

O'Toole A (2021) cov-lineages. org website. Zenodo. https://cov-lineages.org/ (Acessed on 27 Oct 2021)

Ogawa J, Zhu W, Tonnu N, et al. The D614G mutation in the SARS-CoV2 Spike protein increases infectivity in an ACE2 receptor dependent manner. Biorxiv. 2020 doi: 10.1101/2020.07.21.214932. PubMed DOI PMC

Ong SW, Chiew CJ, Ang LW et al (2021) Clinical and virological features of SARS-CoV-2 variants of concern: a retrospective cohort study comparing B. 1.1. 7 (Alpha), B. 1.315 (Beta), and B. 1.617. 2 (Delta). Clin Infect Dis. 10.1093/cid/ciab721 PubMed PMC

Peacock TP, Sheppard CM, Brown JC et al (2021) The SARS-CoV-2 variants associated with infections in India, B. 1.617, show enhanced spike cleavage by furin. Biorxiv. 10.1101/2021.05.28.446163

Planas D, Veyer D, Baidaliuk A, et al. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature. 2021;596:276–280. doi: 10.1038/s41586-021-03777-9. PubMed DOI

Plante JA, Mitchell BM, Plante KS, et al. The variant gambit: COVID’s next move. Cell Host Microbe. 2021;29:508–515. doi: 10.1016/j.chom.2021.02.020. PubMed DOI PMC

Polinski JM, Weckstein AR, Batech Met al (2021) Effectiveness of the single-dose Ad26. COV2. S COVID vaccine. MedRxiv. 10.1101/2021.09.10.21263385

Press Information Bureau (PIB) GoI (2021) Union Health Ministry advises Maharashtra, Kerala and Madhya Pradesh on Delta Plus Variant, currently a Variant of Concern (VOC). https://pib.gov.in/PressReleaseIframePage.aspx?PRID=1729467 (Acessed on 20 Oct 2021)

Rao VU, Arakeri G, Subash A, et al. COVID-19: loss of bridging between innate and adaptive immunity? Med Hypotheses. 2020;144:109861. doi: 10.1016/j.mehy.2020.109861. PubMed DOI PMC

Salehi-Vaziri M, Jalali T, Farahmand B, et al. Clinical characteristics of SARS-CoV-2 by re-infection vs. reactivation: a case series from Iran. Eur J Clin Microbiol Infect Dis. 2021;40:1713–1719. doi: 10.1007/s10096-021-04221-6. PubMed DOI PMC

Shastri J, Parikh S, Aggarwal V et al (2021) Severe SARS-CoV-2 breakthrough reinfection with Delta variant after recovery from breakthrough infection by Alpha variant in a fully vaccinated health worker. Front Med 1379 PubMed PMC

Shu Y, McCauley J. GISAID: Global initiative on sharing all influenza data–from vision to reality. Euro Surveill. 2017;22:30494. doi: 10.2807/1560-7917.ES.2017.22.13.30494. PubMed DOI PMC

Singanayagam A, Patel M, Charlett A, et al. Duration of infectiousness and correlation with RT-PCR cycle threshold values in cases of COVID-19, England, January to May 2020. Euro Surveill. 2020;25:2001483. doi: 10.2807/1560-7917.ES.2020.25.32.2001483. PubMed DOI PMC

Tchesnokova V, Kulasekara H, Larson L, et al. Acquisition of the L452R mutation in the ACE2-binding interface of Spike protein triggers recent massive expansion of SARS-Cov-2 variants. J Clin Microbiol. 2021;59:e00921–e1021. doi: 10.1128/JCM.00921-21. PubMed DOI PMC

Vaidyanathan G. Coronavirus variants are spreading in India—what scientists know so far. Nature. 2021;593:321–322. doi: 10.1038/d41586-021-01274-7. PubMed DOI

Volz E, Hill V, McCrone JT, et al. Evaluating the effects of SARS-CoV-2 spike mutation D614G on transmissibility and pathogenicity. Cell. 2021;184(64–75):e11. PubMed PMC

Walensky RP, Walke HT, Fauci AS. SARS-CoV-2 variants of concern in the United States—challenges and opportunities. JAMA. 2021;325:1037–1038. doi: 10.1001/jama.2021.2294. PubMed DOI PMC

Wang L, Gao GF. The “Wolf” is indeed coming: recombinant “Deltacron” SARS-CoV-2 detected. China CDC Weekly. 2022;4:285. doi: 10.46234/ccdcw2022.054. PubMed DOI PMC

Wang Y, Chen R, Hu F, et al. Transmission, viral kinetics and clinical characteristics of the emergent SARS-CoV-2 Delta VOC in Guangzhou, China. Eclinicalmedicine. 2021;40:101129. doi: 10.1016/j.eclinm.2021.101129. PubMed DOI PMC

Weisblum Y, Schmidt F, Zhang F, et al. Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. Elife. 2020;9:e61312. doi: 10.7554/eLife.61312. PubMed DOI PMC

Wrenn JO, Pakala SB, Vestal G et al (2022) COVID-19 severity from Omicron and Delta SARS-CoV-2 variants. Viruses, Influenza and Other Respiratory. 10.1111/irv.12982 PubMed PMC

Yadav PD, Sapkal GN, Abraham P, et al. Neutralization of variant under investigation B. 1.617 with sera of BBV152 vaccinees. Clin Infect Dis. 2021;72:366–368. PubMed

Yi C, Sun X, Ye J, et al. Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies. Cell Mol Immunol. 2020;17:621–630. doi: 10.1038/s41423-020-0458-z. PubMed DOI PMC

Zhang J, Xiao T, Cai Y, et al. Membrane fusion and immune evasion by the spike protein of SARS-CoV-2 Delta variant. Science. 2021;374:1353–1360. doi: 10.1126/science.abl9463. PubMed DOI PMC