Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of the coronavirus disease 2019 (COVID-19), has caused more than 179 million infections and 3.8 million deaths worldwide. Throughout the past year, multiple vaccines have already been developed and used, while some others are in the process of being developed. However, the emergence of new mutant strains of SARS-CoV-2 that have demonstrated immune-evading characteristics and an increase in infective capabilities leads to potential ineffectiveness of the vaccines against these variants. The purpose of this review article is to highlight the current understanding of the immunological mechanisms of the virus and vaccines, as well as to investigate some key variants and mutations of the virus driving the current pandemic and their impacts on current management guidelines. We also discussed new technologies being developed for the prevention, treatment, and detection of SARS-CoV-2. In this paper, we thoroughly reviewed and provided crucial information on SARS-CoV-2 virology, vaccines and drugs being used and developed for its prevention and treatment, as well as important variant strains. Our review paper will be beneficial to health care professionals and researchers so they can have a better understanding of the basic sciences, prevention, and clinical treatment of COVID-19 during the pandemic. This paper consists of the most updated information that has been available as of June 21, 2021.
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Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun, 2020,109:102433
Hatmal MM, Alshaer W, Al-Hatamleh MAI, 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(12):2638
Masters PS. Coronavirus genomic RNA packaging. Virology, 2019,537:198–207
Kaur N, Singh R, Dar Z, et al. Genetic comparison among various coronavirus strains for the identification of potential vaccine targets of SARS-CoV2. Infect Genet Evol, 2021,89:104490
Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 2020,579(7798):270–273
Bai C, Warshel A. Critical Differences between the Binding Features of the Spike Proteins of SARS-CoV-2 and SARS-CoV. J Phys Chem B, 2020,124(28):5907–5912
Huang Y, Yang C, Xu XF, et al. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin, 2020,41(9):1141–1149
Ozono S, Zhang Y, Ode H, et al. SARS-CoV-2 D614G spike mutation increases entry efficiency with enhanced ACE2-binding affinity. Nat Commun, 2021,12(1):848
Rahman N, Basharat Z, Yousuf M, et al. Virtual Screening of Natural Products against Type II Transmembrane Serine Protease (TMPRSS2), the Priming Agent of Coronavirus 2 (SARS-CoV-2). Molecules, 2020,25(10):2271
Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell, 2020,181(2):271–80.e8
Zhou Z, Zhao N, Shu Y, et al. Effect of Gastrointestinal Symptoms in Patients With COVID-19. Gastroenterology, 2020,158(8):2294–2297
Perisetti A, Goyal H, Gajendran M, et al. Prevalence, Mechanisms, and Implications of Gastrointestinal Symptoms in COVID-19. Front Med, 2020,7:588711
O’Hearn M, Liu J, Cudhea F, et al. Coronavirus Disease 2019 Hospitalizations Attributable to Cardiometabolic Conditions in the United States: A Comparative Risk Assessment Analysis. J Am Heart Assoc, 2021,10(5): e019259
Caramelo F, Ferreira N, Oliveiros B. Estimation of risk factors for COVID-19 mortality— preliminary results. medRxiv, 2020,02.24.20027268
Gheblawi M, Wang K, Viveiros A, et al. Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System: Celebrating the 20th Anniversary of the Discovery of ACE2. Circ Res, 2020,126(10):1456–1474
Coperchini F, Chiovato L, Croce L, et al. The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system. Cytokine Growth Factor Rev, 2020,53:25-32
Faqihi F, Alharthy A, Memish ZA, et al. Comment on Hu et al: The cytokine storm and COVID-19. J Med Virol, 2021,93(2):631–633
Biswas S, Thakur V, Kaur P, et al. Blood clots in COVID-19 patients: Simplifying the curious mystery. Med Hypotheses, 2021,146:110371
Huang Q, Wu X, Zheng X, et al. Targeting inflammation and cytokine storm in COVID-19. Pharmacol Res, 2020,159:105051
Tay MZ, Poh CM, Rénia L, et al. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol, 2020,20(6):363–374
Zheng HY, Zhang M, Yang CX, et al. Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients. Cell Mol Immunol, 2020,17(5):541–543
Chowdhury MA, Hossain N, Kashem MA, et al. Immune response in COVID-19: A review. J Infect Public Health, 2020,13(11):1619–1629
Lee WS, Wheatley AK, Kent SJ, et al. Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies. Nat Microbiol, 2020,5(10):1185–1191
Tirado SM, Yoon KJ. Antibody-dependent enhancement of virus infection and disease. Viral Immunol, 2003,16(1):69–86
Ricke DO. Two Different Antibody-Dependent Enhancement (ADE) Risks for SARS-CoV-2 Antibodies. Front Immunol, 2021,12:640093
Huang Q, Zeng J, Yan J. COVID-19 mRNA vaccines. J Genet Genomics, 2021,48(2):107–114
Livingston EH, Malani PN, Creech CB. The Johnson & Johnson Vaccine for COVID-19. JAMA, 2021,325(15): 1575
Al Kaabi N, Zhang Y, Xia S, et al. Effect of 2 Inactivated SARS-CoV-2 Vaccines on Symptomatic COVID-19 Infection in Adults: A Randomized Clinical Trial. JAMA, 2021, e218565. doi: https://doi.org/10.1001/jama.2021.8565. Epub ahead of prrnt. PMID: 34037666; PMCID: PMC8156175.
Xia S, Zhang Y, Wang Y, et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial. Lancet Infect Dis, 2021,21(1):39–51
Wu Z, Hu Y, Xu M, et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect Dis, 2021,21(6):803–812
Xu S, Yang K, Li R, et al. mRNA Vaccine Era-Mechanisms, Drug Platform and Clinical Prospection. Int J Mol Sci, 2020,21(18):6582
Cagigi A, Loré K. Immune Responses Induced by mRNA Vaccination in Mice, Monkeys and Humans. Vaccines, 2021,9(1):61
Linares-Fernández S, Lacroix C, Exposito JY, et al. Tailoring mRNA Vaccine to Balance Innate/Adaptive Immune Response. Trends Mol Med, 2020,26(3):311–323
Schoenmaker L, Witzigmann D, Kulkarni JA, et al. mRNA-lipid nanoparticle COVID-19 vaccines: Structure and stability. Int J Pharm, 2021,601:120586
Dyer O. Covid-19: EMA defends AstraZeneca vaccine as Germany and Canada halt rollouts. BMJ, 2021,373: n883
Xia S, Duan K, Zhang Y, et al. Effect of an Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity Outcomes: Interim Analysis of 2 Randomized Clinical Trials. JAMA, 2020,324(10):951–960
Zhang Y, Zeng G, Pan H, et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18–59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect Dis, 2021,21(2):181–192
Golob JL, Lugogo N, Lauring AS, et al. SARS-CoV-2 vaccines: a triumph of science and collaboration. JCI Insight, 2021,6(9):149187
Zhu FC, Li YH, Guan XH, et al. Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial. Lancet, 2020,395(10240):1845–1854
Mallapaty S. China’s COVID vaccines are going globalbut questions remain. Nature, 2021,593(7858):178–179
Logunov DY, Dolzhikova IV, Shcheblyakov DV, et al. Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia. Lancet, 2021,397(10275):671–681
Logunov DY, Dolzhikova IV, Zubkova OV, et al. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. Lancet, 2020,396(10255):887–897
Chung YH, Beiss V, Fiering SN, et al. COVID-19 Vaccine Frontrunners and Their Nanotechnology Design. ACS Nano, 2020,14(10):12 522–12 537
Wadman M. The long shot. Science, 2020,370(6517):649–653
Medhi R, Srinoi P, Ngo N, et al. Nanoparticle-Based Strategies to Combat COVID-19. ACS Appl Nano Mater, 2020,3(9)8557–8580
Ashraf MU, Kim Y, Kumar S, et al. COVID-19 Vaccines (Revisited) and Oral-Mucosal Vector System as a Potential Vaccine Platform. Vaccines, 2021,9(2):171
Moore AC, Dora EG, Peinovich N, et al. Preclinical studies of a recombinant adenoviral mucosal vaccine to prevent SARS-CoV-2 infection. bioRxiv, 2020.09.04.283853; doi: https://doi.org/10.1101/2020.09.04.283853
Cubuk J, Alston JJ, Incicco JJ, et al. The SARS-CoV-2 nucleocapsid protein is dynamic, disordered, and phase separates with RNA. Nat Commun, 2021,12(1):1936
Nooraei S, Bahrulolum H, Hoseini ZS, et al. Viruslike particles: preparation, immunogenicity and their roles as nanovaccines and drug nanocarriers. J Nanobiotechnology, 2021,19(1):59
Mahmood N, Nasir SB, Hefferon K. Plant-Based Drugs and Vaccines for COVID-19. Vaccines, 2020,9(1):15
Khoury DS, Cromer D, Reynaldi A, et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat Medicine, 2021. doi: https://doi.org/10.1038/s41591-021-01377-8. Epub ahead of print. PMID: 34002089.
Wu K, Werner AP, Koch M, et al. Serum Neutralizing Activity Elicited by mRNA-1273 Vaccine. N Engl J Med, 2021,384(15):1468–1470
van Oosterhout C, Hall N, Ly H, et al. COVID-19 evolution during the pandemic— Implications of new SARS-CoV-2 variants on disease control and public health policies. Virulence, 2021,12(1):507–508
Abdool Karim SS, de Oliveira T. New SARS-CoV-2 Variants—Clinical, Public Health, and Vaccine Implications. N Engl J Med, 2021,384(19):1866–1868
Zou J, Xie X, Fontes-Garfias CR, et al. The effect of SARS-CoV-2 D614G mutation on BNT162b2 vaccrne-elicited neutralization. NPJ Vaccines, 2021,6(1):44
Korber B, Fischer WM, Gnanakaran S, et al. Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus. Cell, 2020,182(4):812–827.e19
Plante JA, Liu Y, Liu J, et al. Spike mutation D614G alters SARS-CoV-2 fitness. Nature, 2021,592(7852):116–121
Planas D, Bruel T, Grzelak L, et al. Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies. Nat Med, 2021,27(5):917–924
Shen X, Tang H, McDanal C, et al. SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral spike vaccines. Cell Host Microbe, 2021,29(4):529–539.e3
Supasa P, Zhou D, Dejnirattisai W, et al. Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera. Cell, 2021,184(8):2201–2211.e7
Zhou H, Dcosta BM, Samanovic MI, et al. B.1.526 SARS-CoV-2 variants identified in New York City are neutralized by vaccine-elicited and therapeutic monoclonal antibodies. bioRxiv, 2021.03.24.436620; doi: https://doi.org/10.1101/2021.03.24.436620
Annavajhala MK, Mohri H, Zucker JE, et al. A Novel SARS-CoV-2 Variant of Concern, B.1.526, Identified in New York. medRxiv, 2021.02.23.21252259. doi: https://doi.org/10.1101/2021.02.23.21252259
Greaney AJ, Loes AN, Crawford KHD, et al. Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies. Cell Host Microbe, 2021,29(3):463–476.e6
Kuzmina A, Khalaila Y, Voloshin O, et al. SARS-CoV-2 spike variants exhibit differential infectivity and neutralization resistance to convalescent or postvaccination sera. Cell Host Microbe, 2021,29(4):522–528.e2
Edara VV, Norwood C, Floyd K, et al. Infection- and vaccine-induced antibody binding and neutralization of the B.1.351 SARS-CoV-2 variant. Cell Host Microbe, 2021,29(4):516–521.e3
Shinde V, Bhikha S, Hoosain Z, et al. Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant. N Engl J Med, 2021,384(20):1899–1909
Madhi SA, Baillie V, Cutland CL, et al. Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant. N Engl J Med, 2021,384(20):1885–1898
Toovey OTR, Harvey KN, Bird PW, et al. Introduction of Brazilian SARS-CoV-2 484K.V2 related variants into the UK. J Infect, 2021,82(5):e23–e4
Sapkal G, Yadav PD, Ella R, et al. Neutralization of B.1.1.28 P2 variant with sera of natural SARS-CoV-2 infection and recipients of BBV152 vaccine. bioRxiv, 2021,04.30.441559. doi: https://doi.org/10.1101/2021.04.30.441559
Garcia-Beltran WF, Lam EC, St Denis K, et al. Circulating SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity. medRxiv, 2021.02.14.21251704. doi: https://doi.org/10.1101/2021.02.14.21251704
Hirotsu Y, Omata M. Discovery of SARS-CoV-2 strain of P.1 lineage harboring K417T/E484K/N501Y by whole genome sequencing in the city, Japan. medRxiv, 2021.02.24.21251892. doi: https://doi.org/10.1101/2021.02.24.21251892
Dejnirattisai W, Zhou D, Supasa P, et al. Antibody evasion by the P.1 strain of SARS-CoV-2. Cell, 2021, 184(11):2939–2954
Cherian S, Potdar V, Jadhav S, et al. Convergent evolution of SARS-CoV-2 spike mutations, L452R, E484Q and P681R, in the second wave of COVID-19 in Maharashtra, India. bioRxiv, 2021.04.22.440932. doi: https://doi.org/10.1101/2021.04.22.440932
Motozono C, Toyoda M, Zahradnik J, et al. An emerging SARS-CoV-2 mutant evading cellular immunity and increasing viral infectivity. bioRxiv, 2021.04.02.438288. doi: https://doi.org/10.1101/2021.04.02.438288
Deng X, Garcia-Knight MA, Khalid MM, et al. Transmission, infectivity, and antibody neutralization of an emerging SARS-CoV-2 variant in California carrying a L452R spike protein mutation. medRxiv, 2021.03.07.21252647. doi: https://doi.org/10.1101/2021.03.07.21252647
Nazir SUR, Nazir T, Sultana M, et al. The Potentially Recommended Pharmacotherapy for COVID-19. Altern Ther Health Med, 2021,27(S1):24–28
Drożdżal S, Rosik J, Lechowicz K, et al. FDA approved drugs with pharmacotherapeutic potential for SARS-CoV-2 (COVID-19) therapy. Drug Resist Updat, 2020,53:100719
Kokic G, Hillen HS, Tegunov D, et al. Mechanism of SARS-CoV-2 polymerase stalling by remdesivir. Nat Commun, 2021,12(1):279
Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the Treatment of Covid-19—Final Report. N Engl J Med, 2020,383(19):1813–1826
White KM, Rosales R, Yildiz S, et al. Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A. Science, 2021, 371(6532):926–931
Martinez MA. Plitidepsin: a Repurposed Drug for the Treatment of COVID-19. Antimicrob Agents Chemother, 2021,65(4)e00200–21
Cox RM, Wolf JD, Plemper RK. Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets. Nat Microbiol, 2021,6(1):11–18
Gottlieb RL, Nirula A, Chen P, et al. Effect of Bamlanivimab as Monotherapy or in Combination With Etesevimab on Viral Load in Patients With Mild to Moderate COVID-19: A Randomized Clinical Trial. JAMA, 2021,325(7):632–644
Deb P, Molla MMA, Saif-Ur-Rahman KM. An update to monoclonal antibody as therapeutic option against COVID-19. Biosafety Health, 2021,3(2):87–91
Li R, Ma X, Deng J, et al. Differential efficiencies to neutralize the novel mutants B.1.1.7 and 501Y.V2 by collected sera from convalescent COVID-19 patients and RBD nanoparticle-vaccinated rhesus macaques. Cell Mol Immunol, 2021,18(4):1058–1060
Acharya KP, Ghimire TR, Subramanya SH. Access to and equitable distribution of COVID-19 vaccine in low-income countries. NPJ Vaccines, 2021,6(1):54
Quast I, Tarlinton D. B cell memory: understanding COVID-19. Immunity, 2021,54(2):205–210
Rahimi H, Salehiabar M, Barsbay M, et al. CRISPR Systems for COVID-19 Diagnosis. ACS Sens, 2021, 6(4):1430–1445
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Forchette, L., Sebastian, W. & Liu, T. A Comprehensive Review of COVID-19 Virology, Vaccines, Variants, and Therapeutics. CURR MED SCI 41, 1037–1051 (2021). https://doi.org/10.1007/s11596-021-2395-1
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DOI: https://doi.org/10.1007/s11596-021-2395-1