studies demonstrated reduced vaccine efficacy against B.1.351, it is likely that the efficacy against P. 1 strain is reduced [47]. Sinovac Biotech has initiated the clinical trials which demonstrated that the CoronoVac vaccine is 50% effective in preventing infection with the P.1 variant in Brazil [47]. B.1.526 and B.1.525 have a reduction in vaccine efficacy [15]. Further studies are required to study the efficacy of the current approved vaccines against the double mutant variant [40, 47]. According to Indian Council of Medical Research Virology Lab, Bharat Biotech’s COVAXIN vaccine has been found to effectively neutralize the infection, and is 78% effective against the double mutant variant [39-41]. COVID-19 Vaccine Challenges Though COVID-19 vaccines are an effective critical tool, none of them are a 100% effective in the prevention of COVID-19 illness. A small percentage of the fully immunized population will still get sick to varying degrees from COVID-19 disease. They are known as vaccine breakthrough cases. A person who has SARS-CoV-2 RNA or antigen detected on a respiratory specimen collected on or after 14 days after completing the primary series of a US FDA-authorized COVID-19 vaccine fits the definition of a vaccine breakthrough case. More than 75 million people have been fully vaccinated as of April 13, 2021 since December 14, 2020. During the same duration, there have been 5,814 vaccine breakthrough cases reported across the USA. Forty-five percent of the total cases were female, 29% were asymptomatic, 45% were over 60 years of age, 7% of the total cases were hospitalized, and 1% died [48]. There have been several hurdles in general to vaccine administration. Pregnant and breastfeeding women, immunocompromised, diverse race and ethnicities have been underrepresented populations in vaccines studies. Vaccine refusal has been an issue physicians have had to deal with even in pre-pandemic times [49]. There has been growing COVID-19 vaccine hesitancy [50]. Equitable vaccine distribution, storage requirements and cost are factors that will have a significant impact in areas across the world. Conclusions The emerging variants not only result in increased transmissibility, morbidity and mortality but also have the ability to evade detection by diagnostic tests, exhibit decreased susceptibility to treatment including antivirals, monoclonal antibodies and convalescent plasma, possess the ability to cause reinfection in previously recovered and vaccinated individuals. Children and immunocompromised individuals are at increased risk of developing multisystem inflammatory syndrome or long-haul COVID [51, 52]. The longer the virus propagates the chance of mutations are higher. Vaccine breakthrough cases are often undercounted and fully vaccinated populations should still practice preventative measures. At the time of this paper 40.7% of the total population in the USA was fully vaccinated. The USA ranks eighth in terms of percentage of population vaccinated. Israel ranks first with 57% of the total population vaccinated followed by Bahrain and Aruba [53, 54]. Continuation Articles © The authors | Journal compilation © J Clin Med Res and Elmer Press Inc™ | www.jocmr.org 323 Vasireddy et al J Clin Med Res. 2021;13(6):317-325 of precautionary measures including masking, hand hygiene, isolation and quarantine along with other public health mitigation strategies, genomic surveillance and vaccination plays an important role in prevention of spread; early identification of variants, prevention of mutations and viral replication, respectively, and still form the cornerstone of the action plan to control the COVID-19 pandemic [55]. Acknowledgments None to declare. Financial Disclosure The authors declare that they do not have a financial relationship with any commercial entity that has an interest in the subject of this manuscript. No grants were obtained for this study. Conflict of Interest The authors declare that they do not have a conflict of interest. Author Contributions DV, RV, GM, SVM and PA performed literature search. DV and RV drafted the manuscript. DV, RV, GM, SVM and PA did critical editing. DV and RV contributed to the illustrations. DV and RV carefully supervised this manuscript preparation and writing. Data Availability The authors declare that data supporting the findings of this study are available within the article. Abbreviations SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; RNA: ribonucleic acid; WHO: World Health Organisation; CSG: Coronavirus Research Group; N: nucleocapsid; M: membrane; S: spike; E: envelope; nsp14: nonstructural protein 14; ACE2: angiotensin-converting enzyme 2; RdRp: RNA-dependent RNA polymerase; GISAID: Global Influenza Surveillance and Response System; NIID: National Institute of Infectious Diseases; CDC: Center of Disease Control and Prevention; NTD: non-terminal domain; mRNA: messenger RNA; DNA: deoxyribonucleic acid References 1. Klein S, Cortese M, Winter SL, Wachsmuth-Melm M, Res. 2021;13(6):317-325 rus/variants/. Accessed June 10, 2021. 18. How the flu virus can change: "Drift" and "Shift". Centers for Disease Control and Prevention. https://www.cdc. gov/flu/about/viruses/change.htm. Published October 15, 2019.. COVID-19 epidemic in the Brazilian state of Amazonas was driven by long-term persistence of endemic SARSCoV-