the distinguishing feature of a coronavirus is its:

CAS 26, 14221427 (2020). Kustin, T. et al. "As a council member, I'm disappointed and appalled that no one else would think that there was anything wrong with this report," said Jones, a Democrat who represents District 2. Adv. Ke, Z. et al. Mol. Preprint at https://www.medrxiv.org/content/10.1101/2021.05.07.21256809v1 (2021). Science 369, 77 (2020). It has been speculated that pre-existing PEG antibodies might be involved in these allergic events124. Published information about the production process is available for two inactivated whole-virus vaccines manufactured by the Chinese companies Sinopharm and Sinovac (Table1). Shimizu, K., Sakurai, F., Machitani, M., Katayama, K. & Mizuguchi, H. Quantitative analysis of the leaky expression of adenovirus genes in cells transduced with a replication-incompetent adenovirus vector. Heterologous prime-boost COVID-19 vaccination: initial reactogenicity data. Independent of such antigenic effects, the fundamentally different mechanisms of action and ways of production are likely to introduce additional variation to the characteristics of immune responses and possible adverse reactions. 7, 748756 (2021). (Image credit: Daedalean) Daedalean is looking to get its AI certified with both the FAA (Federal Aviation Administration) and EASA (European Union Aviation Safety Agency . To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. 21, 637646 (2021). Although in vitro model studies with one of the current adenovirus vector vaccines (ChAdOx1 nCoV-19; Table1) have shown that S-coding transcripts dominate the transcription patterns, rare aberrant splicing or polyadenylation site usage were observed72. . Zhu, F.-C. et al. 100, 309354 (2018). Manish Sadarangani, Arnaud Marchant & Tobias R. Kollmann, Samir Andrade Mendona, Reka Lorincz, David T. Curiel, Nikolaos C. Kyriakidis, Andrs Lpez-Corts, Esteban Ortiz Prado, Guido Forni, Alberto Mantovani & on behalf of the COVID-19 Commission of Accademia Nazionale dei Lincei, Rome, Milja Belik, Pinja Jalkanen, Ilkka Julkunen, Aileen Ebenig, Mona V. Lange & Michael D. Mhlebach, Neeltje van Doremalen, Jonathan E. Schulz, Vincent J. Munster, Chih-Jung Chen, Lan-Yan Yang, Kuan-Ying A. Huang, Simon P. Graham, Rebecca K. McLean, Teresa Lambe, npj Vaccines Watanabe, Y. et al. 888-535-6136. Heinz, F. X. 7, 594602 (2021). Potently neutralizing and protective human antibodies against SARS-CoV-2. Distinguishing viral pneumonia from bacterial pneumonia is difficult in the community. Preprint at https://www.researchsquare.com/article/rs-440461/v1 (2021). . The first category consists of mRNA and adenoviral vector vaccines (herein referred to as genetic vaccines, sections: Genetic vaccinesgeneral, mRNA vaccines, Adenovirus-vector vaccines), both of which do not contain the spike protein but provide genetic information for its biosynthesis in body cells of the vaccinee. A distinguishing feature of SARSCoV2 is its incorporation of a polybasic site cleaved by furin, which appears to be an important element enhancing its virulence. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Nature 584, 437442 (2020). 10, 28752884 (2014). Development of an inactivated vaccine candidate, BBIBP-CorV, with potent protection against SARS-CoV-2. The precise mechanisms of how the RNA is taken up by different cells after vaccination and escapes from LNPs and intracellular vesicles is incompletely resolved53,55. High rates of seropositivity against adenovirus 5 (the pioneer of adenovirus vector development) have been reported in the population126,127, and a number of studies have shown that pre-existing vector immunity can impair the response to the vaccine antigen128,129,130. Adenovirus 5 is used in the CanSino vaccine and the second dose of Gamaleya vaccines (section Adenovirus-vector vaccines and Table1). AZD1222-induced neutralising antibody activity against SARS-CoV-2 Delta VOC. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Lancet 397, 16461657 (2021). It is believed (but not systematically studied and formally shown) that muscle cells, fibroblasts, endothelial cells, and/or immune cells such as dendritic cells contribute to the expression of S after intramuscular vaccination40,41,42. Bangaru, S. et al. Lancet https://doi.org/10.1016/s0140-6736(21)01462-8 (2021). Animal experiments have shown that adenovirus-vector DNA can remain detectable for months after inoculation in transcriptionally active form82 in contrast to rapidly degraded RNA55,83. Google Scholar. Zeng, C., Zhang, C., Walker, P. G. & Dong, Y. Formulation and delivery technologies for mRNA vaccines. Both vaccines use aluminum hydroxide as an adjuvant. . Luckily, Apple is known for its uncompromising screen standards, and the new iPad and iPad Air are no different. However, the authors discuss evidence of shedding of the cleaved S1 portion78, which has also been observed in model studies with unmodified S proteins compared to mutationally stabilized proteins18 (Fig. Vaccine 39, 21902200 (2021). A team of researchers from the National Library of Medicine (NLM), part of the National Institutes of Health, identified genomic features of SARS-CoV-2, the virus that causes COVID-19, and other high-fatality coronaviruses that distinguish them from other members of the coronavirus family. Logunov, D. Y. et al. The severe consequences of the COVID-19 pandemic have created a pressing need for vaccines that not only prevent serious disease but preferentially also transmission. Investig. Ma, J. et al. The trigger comprises binding of RBD to ACE2 and a further proteolytic cleavage by cellular proteases (in addition to the furin cleavage between S1 and S2) at the so-called S2 site, resulting in the removal of a small sequence element and the exposure of the fusion peptide at the N-terminus of S2 (Fig. Science 372, 1108 (2021). Pardi, N., Hogan, M. J., Porter, F. W. & Weissman, D. mRNA vaccinesa new era in vaccinology. Chen, N. et al. Curr. Dis. At 10.9 inches, the 4th-generation iPad Air boasts a larger screen than the iPad . You are using a browser version with limited support for CSS. The coronavirus and its variants are very contagious. PLoS ONE 7, e40385 (2012). Science Translational Medicine. Lancet 397, 18191819 (2021). Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Article Recently, data from a phase 3 clinical trial became available, showing a relatively low efficacy of 47% at preventing disease (https://www.curevac.com/en/2021/06/16/curevac-provides-update-on-phase-2b-3-trial-of-first-generation-covid-19-vaccine-candidate-cvncov/), well below the efficacies reported for the BionTech-Pfizer and Moderna vaccines46,47 and below the requirement of at least 50% efficacy proposed by WHO (https://www.who.int/publications/m/item/considerations-for-the-assessment-of-covid-19-vaccines-for-listing-by-who). ChAdOx1 and MVA based vaccine candidates against MERS-CoV elicit neutralising antibodies and cellular immune responses in mice. After vaccination with mRNA vaccines, rare events of anaphylactic shock above the average incidence in the population have been reported, largely in individuals with a history of allergy123,124. The research team ran two studies, enlisting 1700 adults. The relevance of these differences for protection are not yet clear. Tatsis, N. et al. Wang, H. et al. Lancet 397, 99111 (2021). Shaw, R. H. et al. As outlined in the preceding sections, substantial differences appear to exist among current vaccines that can affect the conformation of S and its presentation to the immune system. Greaney, A. J. et al. PubMedGoogle Scholar. ; Approval of final manuscript: F.X.H. 2d)19. Expert Rev. Antiviral Res 176, 104742104742 (2020). and K.S. The recovery count is 11,35,489 and the active caseload is 11, the Brihanmumbai Municipal Corporation official said. Science 369, 1586 (2020). PubMed A review of the challenges assessing the clinical efficacy of vaccines against SARS-CoV-2. Nature 594, 483 (2021). Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein. Thiagarajan, K. Covid-19: India is at centre of global vaccine manufacturing, but opacity threatens public trust. Understanding of COVID-19 is evolving. The production process of vaccine mRNAs involves the cloning of the corresponding sequence into a plasmid DNA containing a DNA-dependent RNA-polymerase promoter. N. Engl. The unifying feature of all current adenovirus-vaccine vectors is the replacement of one of the early adenoviral genes (E1) for the full-length SARS-Cov-2 S gene in the adenoviral DNA (Fig. Dis. The spikes are the most distinguishing feature of coronaviruses and are responsible for the corona- or halo-like surface. BNT162b vaccines protect rhesus macaques from SARS-CoV-2. N. Engl. Some manufacturers have therefore introduced stabilizing mutations that are intended to prevent inadvertent structural conversion of the labile S protein. Both constructs include the two stabilizing mutations in S2 (K986P and V987P) that were shown to prevent the conformational change of the pre-fusion into the post-fusion structure of S (section Introduction and Fig. ISSN 2059-0105 (online). Dis. Google Scholar. Our review is limited to those vaccines in current use for which phase 3 clinical efficacy data have been reported, and for which published information on the nature and manufacturing process exists. Prefusion RSV F immunization elicits Th2-mediated lung pathology in mice when formulated with a Th2 (but not a Th1/Th2-balanced) adjuvant despite complete viral protection. And like other coronaviruses that infect people, the new coronavirus causes respiratory disease, among other symptoms. Wiener Klinische Wochenschrift 133, 271283 (2021). Wrapp, D. et al. Cell 184, 18211835.e1816 (2021). Dev. J. Med.383, 26032615 (2020). Opin. Front. 48, 6572 (2021). Nature 588, 498502 (2020). Lancet Respiratory Med. Human neutralizing antibodies against SARS-CoV-2 require intact Fc effector functions for optimal therapeutic protection. The domains were colored according to reference.20. Club-shaped glycoprotein spikes in the envelope give the viruses a crownlike, or coronal, appearance. Nat. J. Extremely potent human monoclonal antibodies from COVID-19 convalescent patients. Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Cai, Y. et al. Another mRNA vaccine, manufactured by the company CureVac (current name CVnCoV; Table1) is in an advanced stage of development56. Structural analysis of full-length SARS-CoV-2 spike protein from an advanced vaccine candidate. It was suggested that the acquisition of the furin-cleavage site in the SARS-CoV-2 S protein was essential for zoonotic transfer to humans. J. Virol. Several studies have been conducted to decide whether the chest X-ray and computed tomography (CT) scans of patients indicate COVID-19. Mapping neutralizing and immunodominant sites on the SARS-CoV-2 spike receptor-binding domain by structure-guided high-resolution serology. Science 369, 643 (2020). 4B, right) and further downstream processes for the removal of cellular components and free viral DNA71. Med. Vasileiou, E. et al. Prevention of infection with the Beta, Gamma and Delta variants might be lower, although evidence indicates substantial protection from severe disease after two vaccinations110,112,113. Nat. Tian, J.-H. et al. Correspondence to J. Med. The coronavirus at the root of COVID-19 is the newest known member of this family. Ther.Methods Clin. COVID-19 disease caused by the infection of coronavirus strain SARS-CoV-2. The signal sequence is cleaved off by signal peptidase attached to the inner ER membrane, generating the final N-terminus of the viral spike protein (14-QCVNL). b Transfected cells: Biosynthesis of S occurs in the absence of interactions with other viral proteins. SARS-CoV-2 infection can result in the development of a constellation of persistent sequelae following acute disease called post-acute sequelae of COVID-19 (PASC) or Long COVID 1-3.Individuals diagnosed with Long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions 1-3; however, the basic biological mechanisms responsible . The results from a hydrogeological study at LithiumBank Resources Corp (TSX-V:LBNK)'s 100%-owned Park Place lithium brine project, located in Alberta are "surprisingly favorable," according to analysts at Noble Capital.. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. Wall, E. C. et al. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and pathogenic coronavirus that emerged in late 2019 and has caused a pandemic of acute respiratory. Effectiveness of the BNT162b2 Covid-19 Vaccine against the B.1.1.7 and B.1.351 Variants. Graham, C. et al. Similar to mRNA vaccines, adenovirus vector vaccines are intended to result in the production of native S proteins from a specific mRNA in cells of the vaccinee (Figs. Structural impact on SARS-CoV-2 spike protein by D614G substitution. These considerations of vector immunity also prompted the development of non-human adenovirus vectors such as ChAdOx1 derived from chimpanzee adenovirus Y2564, now used in the Oxford-AstraZeneca vaccine77. PEGpolyethyleneglycol. COVID-19 and the flu have many symptoms in common, including: Fever Cough Shortness of breath or difficulty breathing Tiredness Sore throat Runny or stuffy nose Muscle aches Headache Nausea or vomiting, but this is more common in children than in adults The signs and symptoms of both diseases can range from no symptoms to mild or severe symptoms. In addition, background expression of remaining adenoviral genes has been demonstrated in this as well as in other studies with human adenovirus-based vectors72,76. Details of purification procedures of the Bharat vaccine and the degree of cellular contaminants in the Sinopharm vaccine (which is less purified than that of Sinovac according to ref. Similarly, immune responses to protein-based vaccines are shaped by the adjuvant used, for example by shifting CD4 T cells towards either Th1 or Th2118,119. Cell 183, 10241042.e1021 (2020). Zhang, Y. et al. Sci. Like many other viruses, SARS-CoV-2 is an RNA virus. PubMed Lancet Infect. For reducing potential negative effects of pre-existing immunity, alternative adenoviruses were developed as vectors, one of them adenovirus 26, which has lower rates of seropositivity in the population127 and is now used in the Janssen-Johnson&Johnson vaccine19,62 as well as in the first shot of the Gamaleya-Institute vaccine67,68. Lasaro, M. O. For meaningful conclusions, studies on these topics will require head-to-head comparisons of vaccines, and corresponding publications are expected to expand rapidly in the near future. Vaccines (Basel) 9, 326 (2021). The most striking difference is that COVID-19 can cause a loss of sense and smell. mRNA, adenoviral vector as well as inactivated whole-virus vaccines are now in widespread use, and a subunit vaccine is in a final stage of authorization. Phase 1 assessment of the safety and immunogenicity of an mRNA- Lipid nanoparticle vaccine candidate against SARS-CoV-2 in human volunteers. & Verrier, B. Tailoring mRNA vaccine to balance innate/adaptive immune response. Adv. The impact of coronavirus disease 2019 (COVID-19) on healthcare-associated infections in 2020: a summary of data reported to the National Healthcare Safety Network. Nat. Blood 110, 19161923 (2007). Commun. The RNA in this vaccine is also codon-optimized and contains modifications to improve its performance, butdifferent from the BioNTech-Pfizer and Moderna mRNA vaccines described aboveit does not contain the m1 nucleoside modifications57,58. N. Engl. Rossman, H. et al. PubMed Key features of the vaccines discussed in this review are summarized in Table1. a Infected cells: Subgenomic mRNAs for viral structural proteins are translated in association with the ER (S, M, and E) or in the cytoplasm (N), and virus assembly takes place in the ERGIC. 22, 539540 (2021). b Schematic of a lipidnanoparticle (LNP) used for delivery of mRNA vaccines. CAS Details of purification procedures during manufacturing of the current adenovirus vector vaccines may differ but are not published. Trends Biochem. 7, eabe5575 (2021). With this kind of vaccines, the specific design of genetic sequences for the correct formation and presentation of properly folded spike proteins to B cells are in the foreground of interest. Many uncertainties remain in our understanding of the spread of Covid-19 and its management. Curr. Microbiol. BMJ 373, n969 (2021). Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection. 384, 18851898 (2021). Release of newly produced vector particles through cell lysis. Therefore, it is urgent to know the epidemic . Liu, L. et al. Science 369, 650 (2020). Efficient formation of such antibodies by B cells requires helper functions of CD4 T cells that are specifically stimulated by peptides derived from the same antigen in complex with MHCII molecules. 385, 187189 (2021). Efficacy of the ChAdOx1 nCoV-19 Covid-19 vaccine against the B.1.351 variant. Omicron quickly spread around the world, causing a surge of COVID-19 cases in December 2021 and January 2022. Development of an inactivated vaccine candidate for SARS-CoV-2. 1, 2) in tissues after intramuscular application. Both the Pfizer and Moderna vaccines work by giving the body instructions for how to make a harmless protein that is a distinguishing feature of the actual virus so that when or if the vaccinated person gets exposed to the virus, their body already knows what to do to fight it off. Neutralising antibody activity against SARS-CoV-2 VOCs B.1.617.2 and B.1.351 by BNT162b2 vaccination. Lancet Infect. Pardi, N. et al. Specifically developed and improved ionizable lipids are used in the Moderna and Biontech-Pfizer vaccines (designated Lipid H, SM-102 and ALC-0315, respectively), which together with the molar ratios of the lipid components in LNPs play a critical role for RNA delivery54. containing the mutation D614G in S) may be more stable95,96 and therefore could serve as an improved substrate for the production of inactivated vaccines. CAS The SARS-CoV-2 spike glycoprotein biosynthesis, structure, function, and antigenicity: implications for the design of spike-based vaccine immunogens. Nature 595, 344345 (2021). Logunov, D. Y. et al. On November 30, 2021, the U.S. government SARS-CoV-2 Interagency Group (SIG) classified Omicron as a Variant of Concern (VOC). Also, the death rate due to coronavirus infection is fewer as well. Coronavirus disease (COVID-19) / Feature stories; COVID feature stories. Viruses 13, 54 (2021). The impact of COVID-19 on healthcare-associated infections. 65, 1420 (2020). Liu, C. et al. & Ertl, H. C. New insights on adenovirus as vaccine vectors. Pollard, A. J. Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates. 4c). Preprint at https://www.medrxiv.org/content/10.1101/2020.11.09.20228551v1 (2020). Lancet 397, 23312333 (2021). Proc. They are known to cause diseases including the common cold, Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) in humans.In January 2020, China saw an outbreak of a new coronavirus strain now named SARS-CoV-2. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Xia, S. et al. In both instances, the virus is grown in Vero cells and inactivated by beta-propiolactone (BPL), which is used as an inactivating agent for other viral vaccines, including rabies vaccines85. https://doi.org/10.1038/s41541-021-00369-6, DOI: https://doi.org/10.1038/s41541-021-00369-6. BMJ 372, n196 (2021). Article Twitter users slammed a new ad from Hershey's Canada featuring trans woman Fae Johnstone as the face of its "International Woman's Day" campaign. What defines an efficacious COVID-19 vaccine? Kowarz, E. et al. One of the constituents discussed as being causally linked to anaphylaxis is polyethylene glycol (PEG), which is used in the formulation of LNPs that protect the RNA and facilitate its transfer into cells (section mRNA vaccines). Rochelle Walensky, director of the U.S. Centers for Disease Control and Prevention (CDC), during a meeting with President Biden and members of the White House Covid-19 Response Team on the Omicron . Native-like SARS-CoV-2 spike glycoprotein expressed by ChAdOx1 nCoV-19/AZD1222 vaccine. In predynastic Egypt, Atum was a solar deity associated with the sun god Ra . The effect of residual Triton X-100 on structural stability and infection activity of adenovirus particles. | Meaning, pronunciation, translations and examples McCoy, K. et al. All current vaccines that are authorized for general use and for which clinical efficacy data have been published rely on the viral spike protein (S) as an immunogen, either alone orin the case of inactivated virus vaccinestogether with other viral proteins present in the viral particle (see sections below). However, there may be important clues in the history and the examination that can help differentiate the two. Head-to-head comparisons of current mRNA vaccines with respect to possible differences in the efficiency of protein translation, stability or the stimulation of innate responses are not available in the literature. Proteolytic cleavage into S1 and S2 occurs in the TGN similar to that in infected cells, but some shedding of cleaved S1 and conversion of S2 into its post-fusion structure (S2*) may occur in the absence of stabilizing mutations. Ella, R. et al. A number of monoclonal antibodies were isolated from COVID-19 patients and used for antigenic characterization of the S trimer, including 3D structure determinations of complexes between S (or parts thereof) and antibody Fab fragments. Fund. Coronavirus Rumor Control. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Virus particles are transported through the TGN and released from the cells probably via lysosomes. Bos, R. et al. Nat. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial. Kowalczyk, A. et al. Because of its essential functions during viral entry (receptor binding and membrane fusion), the S protein is the major target of antibodies that can potently neutralize the virus. Cell 184, 39363948.e3910 (2021). Med. Preprint at https://www.researchsquare.com/article/rs-558954/v1 (2021). 27, 10551061 (2021). Capone, S. et al. In this case, seropositivity is negligible in Europe (zero in the UK,64) and low in Africa (9% in Gambian adults,64,131). The second category encompasses protein-based approaches, i.e. The pathway to this mRNA however is substantially more complex than with mRNA vaccines because it takes a detour of the adenoviral DNA through the nucleus (where it remains extrachromosomal) and requires a number of additional cellular processes, including RNA transcription and processing (Fig. Our case report highlights the difficulty of distinguishing SARS-CoV-2 infection in the context of PAP, as the chest CT features are similar. Cai, Y. et al. 13, eabi9915. The amount of impurities depends on the purification steps applied in the manufacturing process. 8, 654866 (2021). Innate responses to RNA that enters cells from the outside (such as in RNA virus infections or mRNA vaccination) differ from those stimulated by adenoviruses, because RNA is sensed by other PRRs, including TLR3, TLR7 and TLR8, all located in endosomes134,135. Eichinger, K. M. et al. After completion of translation, the protein remains attached to the ER membrane through a C-terminal membrane anchor, trimerizes and moves to the ER-Golgi intermediate compartment (ERGIC) where virus assembly occurs by budding into the ERGIC lumen (Fig. The loss of the E1 gene abolishes replication competence of the vector. Immunol. Currently, four adenovirus-vector vaccines are in widespread use. The virus that causes COVID-19 is designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); previously, it was referred to as 2019-nCoV. . 383, 23202332 (2020). This is why it's very important that we socially distance from other people, and wear a mask. b Trimeric pre-fusion spike with one RBD in up position. Opin. Control. Although all current vaccines for which phase 3 efficacy data are available rely on the whole viral spike protein as an antigen, its presentation to the immune system is strikingly different not only between genetic vaccines and protein-based vaccines, but also between vaccines within these categories. Details of manufacturing processes may differ between the companies, and subtle product-specific variations of RNA sequences were recently confirmed by comparative analyses of RNA extracted from original vials of the two vaccines (https://github.com/NAalytics/Assemblies-of-putative-SARS-CoV2-spike-encoding-mRNA-sequences-for-vaccines-BNT-162b2-and-mRNA-1273/blob/main/Assemblies%20of%20putative%20SARS-CoV2-spike-encoding%20mRNA%20sequences%20for%20vaccines%20BNT-162b2%20and%20mRNA-1273.docx.pdf). Wall, E. C. et al. & Stiasny, K. Profiles of current COVID-19 vaccines. Coutard, B. et al. Haas, E. J. et al. These also differ with respect to their degree of purity (presence of extraneous proteins from the production process) and other vaccine constituents that can affect immune responses and cause adverse events. Article Schmidt, T. et al. 5a) (https://patents.google.com/patent/CN111218459B/en). proteins that help give the virus its structure and enable it to replicate. Solar deities have been integral in the development of cultures across the world. 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. Burki, T. K. Challenges in the rollout of COVID-19 vaccines worldwide.

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