the distinguishing feature of a coronavirus is its:

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. The production process of vaccine mRNAs involves the cloning of the corresponding sequence into a plasmid DNA containing a DNA-dependent RNA-polymerase promoter. Cell cultures are also used for production of the inactivated whole-virus vaccines (Vero cells) of Sinopharm88, Sinovac86 and Bharat97 as well as for the Novavax subunit vaccine (insect Sf9 cells)99,101 (sections Inactivated vaccines and Subunit vaccines and Table1). Immunol. N. Engl. It usually spreads between people who are in close contact. Immunol. Distinguishing features of current COVID-19 vaccines: knowns and Preprint at https://www.researchsquare.com/article/rs-440461/v1 (2021). Linares-Fernndez, S., Lacroix, C., Exposito, J.-Y. N. Engl. Rev. Wiener Klinische Wochenschrift 133, 271283 (2021). ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques. What defines an efficacious COVID-19 vaccine? ABCNews.com: What to Know About the Symptoms and Treatment of Norovirus 4b)70. Coronavirus (COVID-19) is an enveloped RNA virus that is diversely found in humans and wildlife. J. Med. Lasaro, M. O. Effects of pre-existing and vaccination-induced immunity against the vector are a special feature of adenovirus vector vaccines. 41). Each dose contains 51010 or 101010 adenoviral particles (Table1), which corresponds to 8 or 16g of adenoviral protein (for calculation see ref. JAMA 325, 15621565 (2021). Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines. ; Approval of final manuscript: F.X.H. Nanomaterial delivery systems for mRNA vaccines. Luckily, Apple is known for its uncompromising screen standards, and the new iPad and iPad Air are no different. Here, we briefly discuss existing data and describe distinguishing features that can contribute to differences among vaccine responses independent of the structure and presentation of the S immunogen. Wall, E. C. et al. 3b)53,54. the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Current COVID-19 vaccines present the spike protein in very different ways to the immune system, and two main categories have to be discerned. Virus particles are transported through the TGN and released from the cells probably via lysosomes. Bos, R. et al. 11, 909 (2020). 5G mmWave: Facts and fictions you should definitely - Android Authority Ther. Lancet Infect. 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. During exocytosis, virus particles encounter the protease furin in the trans-Golgi network (TGN), which cleaves the S protein into its membrane-associated S2 subunit and the distal S1 subunit at a characteristic polybasic cleavage site16. Lancet 397, 13511362 (2021). Nat. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial. 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. Section navigation Coronavirus disease (COVID-19) Feature stories Situation reports; Media resources. J. Virol. Development of an inactivated vaccine candidate, BBIBP-CorV, with potent protection against SARS-CoV-2. COVID-19, short for "coronavirus disease 2019," is caused by the novel coronavirus SARS-CoV-2. J. 21, 637646 (2021). Drug Discov. Curr. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. RBDreceptor binding domain; NTDN-terminal domain; FPfusion peptide. A. et al. Some spike molecules, not assembled into virions, are also transported to the plasma membrane despite the presence of an ER retention signal15. and K.S. The mmWave technology is just one technology that 5G networks can use. and K.S. Such factors may contribute to variations in the efficacies reported in clinical trials with current inactivated whole-virus vaccines94. SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice. N. Engl. PubMed 65, 1420 (2020). Corbett, K. S. et al. Article BMJ 373, n958 (2021). & Yan, J. SARS-CoV-2 virus: vaccines in development. Human Coronavirus Types | CDC There is evidence that the Oxford-AstraZeneca vaccine might induce higher levels of specific T cells, whereas mRNA vaccines might induce higher antibody titers115,116,117. Li, Y. et al. While on site, please take precautions to protect yourself and others from Covid-19 by wearing a mask and maintaining social distance as outlined in the Center for Disease Control (CDC) Guidelines. 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. 2d)19. iScience 24, 102298 (2021). Science 372, 466 (2021). Coronaviruses are a large family of viruses, but only seven of its members infect humans. 81, 65946604 (2007). Features, Evaluation, and Treatment of Coronavirus (COVID-19) Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM. The components used for LNP formulation include phospholipids, cholesterol, special cationic (ionizable) lipids and polyethylene glycol (PEGylated) lipids that are mixed in a sophisticated and critical production step (parts of which are not documented in the published literature) to yield the final vaccine53. 2c)22,23,24. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Feature Article: Wondering about Coronavirus? | Children's Hospital of Increasing evidence indicates that neutralizing antibodies are indeed a reliable correlate of protection5,6,7,8,9. Xia, S. et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. Neutralising antibody activity against SARS-CoV-2 VOCs B.1.617.2 and B.1.351 by BNT162b2 vaccination. Science https://doi.org/10.1126/science.abj9106 (2021). Preprint at https://www.medrxiv.org/content/10.1101/2021.05.07.21256809v1 (2021). After amplification in bacterial cells, the plasmid DNA is linearized and impurities are removed before in vitro transcription into RNA. Nature 583, 290295 (2020). Collectively, there are subtle differences between the two vaccines, both with respect to the RNA and the LNP carriers, and a higher amount of RNA per dose is used in the Moderna vaccine (100g) than in the BioNTech-Pfizer vaccine (30g)46,47. Google Scholar. The inactivated whole virus vaccine produced by Bharat (Covaxin, Table1) is adjuvanted with an imidazoquinoline class molecule (IMDG, a TLR 7/8 agonist) adsorbed on aluminum hydroxide gel (Algel-IMDG) that shifts the response towards Th197,141,142. Adv. Igyrt, B. Understanding of COVID-19 is evolving. Electron microscopical pictures of the viral spikes in the Sinovac vaccine have been interpreted differently, either as displaying the pre-fusion structure86 or the post-fusion structure25,92. Phase 1 assessment of the safety and immunogenicity of an mRNA- Lipid nanoparticle vaccine candidate against SARS-CoV-2 in human volunteers. 384, 20922101 (2021). Although the constructs for all four adenovirus-vector vaccines contain the full-length spike protein, there are some differences in construct design with respect to mutations for stabilizing S as well as to the signal peptide at the N-terminus of S that require attention. Coronaviruses | Microbiology Society Some of these mutants are considered Variants of Concern (VOCs) because of their highly efficient transmission, the concomitant replacement of previously circulating strains, and the presence of mutations in the spike protein that can lead to immune escape (https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/). UTRuntranslated region. c Expression of spike in cells of vaccinated individuals. 1a), the S protein is synthesized from one of the viral subgenomic mRNAs and co-translationally transported into the lumen of the endoplasmic reticulum (ER) by the use of a signal sequence at its N-terminus, comprising residues 1 to 13 of its total 1273 amino acids14. Adenoviral vectors contain PAMPs that can be sensed by TLRs at the plasma membrane (TLR2 and TLR4) and the endosomally located TLR9 (reviewed in ref. The coronavirus and its variants are very contagious. There are still small outbreaks of this coronavirus (MERS-CoV) today. The impact of COVID-19 on healthcare-associated infections. ISSN 2059-0105 (online). 2c, d). 6, eaaz6893 (2020). The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade. 7, 594602 (2021). Distinguishing feature definition and meaning - Collins Dictionary Commun. 21, 195197 (2021). Vaccines (Basel) 9, 326 (2021). Several lines of evidence suggest that BPL-inactivation in combination with purification processes can indeed lead to the formation of the post-fusion spike and the concomitant dissociation of S125,92. Therefore, the landscape of vaccines becoming available for general use may expand in the near future. Many uncertainties remain in our understanding of the spread of Covid-19 and its management. 80). SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness. 2). High-resolution structural analysis revealed that the purified protein is stably locked in the preferred pre-fusion conformation, in part as free trimers and in part as multitrimer complexes103. One of Johnson's distinguishing features is his long-standing relationship with the Chicago Teachers Union. Artificial Intelligence Augmentation of Radiologist Performance in COVID-19 is a contagious respiratory disease caused by infection with the virus SARS-CoV-2. Phase 1-2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine. In vitro transcription is followed by several steps of mRNA purification, including the removal of dsRNA, which could lead to an excessive innate immune response and concomitant reactogenicity48,50. Hofman, K., Shenoy, G. N., Chak, V. & Balu-Iyer, S. V. Pharmaceutical aspects and clinical evaluation of COVID-19 vaccines. Both mRNA vaccines have modulated 5 and 3 untranslated sequences to optimize mRNA stability and translation efficiency44,45, and all uridines are replaced by N1-methylpseudouridine (m1) to further increase RNA stability and to reduce innate immune responses (Fig. 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. The effect of dissociation of soluble S1 from the trimer complex on the quality of immune responses is incompletely understood, but some data suggest it may contribute to a higher proportion of non-neutralizing relative to neutralizing antibodies19,81. Kustin, T. et al. Front. Lancet 397, 23312333 (2021). "One of the distinguishing features of norovirus is that it is highly contagious and transmissible, so just a few virus particles can cause someone to be sick," Gandhi told ABCNews.com. Rubin, R. COVID-19 vaccines vs variantsdetermining how much immunity is enough. Viruses 13, 54 (2021). 7, 586593 (2021). Vaccines (Basel) 9, 61 (2021). The current global pandemic, caused by the coronavirus SARS-CoV-2, emerged in December 2019. No, It's Not Surprising That A Nurse Got COVID-19 After His First Front. The team ran the headlines through a rigorous fact checking. McCoy, K. et al. Science 367, 1260 (2020). Omicron quickly spread around the world, causing a surge of COVID-19 cases in December 2021 and January 2022. The research team ran two studies, enlisting 1700 adults. Cell 184, 23162331.e2315 (2021). Control. Adenoviral vectors persist in vivo and maintain activated CD8+ T cells: implications for their use as vaccines. Coronavirus disease 19 (COVID-19) has resulted in an estimated 470,000 deaths worldwide to date. 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). PubMed Central Dolgin, E. CureVac COVID vaccine let-down spotlights mRNA design challenges. The European Union teams up with WHO to boost COVID-19 vaccination coverage in Africa. Wang, H. et al. Janssen-Johnson&Johnson and Gamaleya-Institute use the authentic SARS-CoV-2 S protein signal sequence19,67, whereas CanSino replaced it with that of human tissue plasminogen activator (tPA) (Fig. These are the products (in alphabetical order) of CanSino Biological Inc./Beijing Institute of Biotechnology, Janssen-Johnson&Johnson, Oxford-AstraZeneca and The Gamaleya Institute Moscow (Table1). Several of the 291 candidates listed in the COVID-19 vaccine pipeline by WHO (184 pre-clinical and 107 in clinical development) (https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines, accessed on July 9, 2021), have already reached the market and are used for mass immunization. Coronaviruses were first discovered in the . We also address the grey matter of additional variables, such as ill-defined downstream production processes and purity of vaccines as well as differences in triggering sensors of innate immunity. 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. Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms. Xia, S. et al. Nature 586, 578582 (2020). Article The viruses are circular in shape with spikes on the surface, which appear like a halo when the virus is viewed with a microscope. Sign up for the Nature Briefing newsletter what matters in science, free to your inbox daily. They all proved to exceed initial hopes and maximal expectations of 50 % protection143,144, displaying efficacies in preventing clinical disease of more than 90% in certain instances. Chen, N. et al. 178, 104792104792 (2020). In the BionTech-Pfizer and Moderna vaccines this problem was taken into account by modifications of the RNA sequence and the inclusion of m1 (section mRNA vaccines), which is not contained in CureVacs mRNA vaccine56. A. 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). Verbeke, R., Lentacker, I., De Smedt, S. C. & Dewitte, H. The dawn of mRNA vaccines: The COVID-19 case. Th1 skewed immune response of whole virion inactivated SARS CoV 2 vaccine and its safety evaluation. The degree of purity of the Sinopharm vaccine (referred to as BBIBP-CorV; Table1) is less clear. In predynastic Egypt, Atum was a solar deity associated with the sun god Ra . Zost, S. J. et al. Even though the CT scan is more sensitive to COVID Pneumonia, Chest X-rays used can be for a possible preliminary classification, due to its prevalent usage as a primary diagnostic test. 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. 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. Nat. Tortorici, M. A. et al. Possible remedies are prime-boost regimens as already used for vaccination with the Gamaleya-Institute vaccine (Ad26 followed by Ad5) or combinations with other classes of vaccines such as mRNA vaccines. They all rely on the native viral spike protein (S) of SARS-CoV-2 for inducing potently neutralizing antibodies, but the presentation of this key antigen to the immune system differs substantially between the different categories of vaccines. Jagannathan, P. & Wang, T. T. Immunity after SARS-CoV-2 infections. Acute allergic reactions to mRNA COVID-19 vaccines. The past few decades have seen endemic outbreaks in the form of Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute . JAMA 324, 951960 (2020). NYU scientists: Largest US study of COVID-19 finds obesity the single PubMedGoogle Scholar. Google Scholar. Corbett, K.S. Kids face the same risk of catching it as adults, although the disease is usually milder in children. Franz X. Heinz or Karin Stiasny. Lutz, J. et al. A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2. Nature 584, 437442 (2020). 384, 18851898 (2021). 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.. ; Visualization: F.X.H. Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum. Opin. Article 1b) (as in mRNA and adenovirus vector vaccines as well as for production of recombinant subunit vaccines), the pathway of biosynthesis is very similar. This means that, unlike in humans and other mammals, the genetic material for SARS-CoV-2 is encoded in ribonucleic acid (RNA). Science 372, 525 (2021). SPsignal peptide; SRPsignal recognition particle; tPAtissue plasminogen activator; ERendoplasmic reticulum; C-terC terminus; N-terN terminus. Irrespective of pre-existing immunity, all adenovirus vector vaccines are prone to induce immune responses against the vector particles129. Development of chimpanzee adenoviruses as vaccine vectors: challenges and successes emerging from clinical trials. Corresponding studies are in progress (Com-Cov study: Oxdorf-AstraZeneca and BionTech-Pfizer, launched in February132). When S is synthesized as an isolated protein (Fig. CAS Nature 594, 483 (2021). Microbiol. Suryadevara, N. et al. Google Scholar. 11, 3618 (2020). A comprehensive review of the global efforts on COVID-19 vaccine development. Variations include (but are not limited to) the type of adenovirus used as a vector, genetic modifications of the vector, the cell lines used for vaccine production, procedures for purification, and the specific design of the gene for expressing S (Table1). Adenovirus-vector and mRNA vaccines promote substantially different innate responses that will certainly influence the nature of adaptive immune responses43. Do your part to the stop the spread of rumors by doing three easy things: Find trusted sources of information. Typically, patients will experience fever, cough, muscle pain and then nausea, and/or vomiting, and diarrhea. b Formation of vaccine particles in production cell line complementing E1 from chromosomally integrated E1 gene. A severe complication of COVID-19 is viral pneumonia. 888-535-6136. Johnson's approach to campaigning provides an additional reason for concern. In the meantime, to ensure continued support, we are displaying the site without styles volume6, Articlenumber:104 (2021) The total amount of protein per dose was found to be 35 to 40g, most of which can be assumed to be cellular protein, because the protein of 51010 adenovirus particles per dose would account for only about 8g (for calculation see122). Coronaviruses have enveloped virions (virus particles) that measure approximately 120 nm (1 nm = 10 9 metre) in diameter. Fund. Alum is the most frequently used adjuvant in human vaccines and is used in the Sinopharm and Sinovac vaccines137,138. Brouwer, P. J. M. et al. Persistence of antigen expression may be a distinctive feature of adenovirus vector vaccines, and has been proposed to contribute to induction of sustained immune responses and long-lasting immunity (reviewed in41). The recovery count is 11,35,489 and the active caseload is 11, the Brihanmumbai Municipal Corporation official said. CDC director's ABC News interview remarks about COVID-19 victims with Cagigi, A. The energy gained by the formation of this hairpin-like structure, in which the fusion peptide is juxtaposed to the C-terminal membrane anchor, is the driving force for viral membrane fusion during entry22. 383, 23202332 (2020). Lancet https://doi.org/10.1016/s0140-6736(21)01462-8 (2021). Liang, Z. et al. Ongoing global and regional adaptive evolution of SARS-CoV-2. Google Scholar. The viral RNA is sneaky: its features cause the protein synthesis . Tian, J.-H. et al. 12 October 2022. | Meaning, pronunciation, translations and examples a Schematic of the vaccine mRNA in BionTech-Pfizer and Moderna vaccines. 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. Blood 110, 19161923 (2007). IUBMB Life 69, 297304 (2017). Ella, R. et al. Get the most important science stories of the day, free in your inbox. 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. Correct processing of the signal peptide by signal peptidase to generate the final N-terminus of S (Fig. Walls, A. C. et al. The images or other third party material in this article are included in the articles Creative Commons license, unless indicated otherwise in a credit line to the material. Studies are emerging that address antibody formation to the different domains of S and analyze the ratio of neutralizing and non-neutralizing antibodies as an important parameter of vaccine performance145,146. Efficacy of the ChAdOx1 nCoV-19 Covid-19 vaccine against the B.1.351 variant. A review of the challenges assessing the clinical efficacy of vaccines against SARS-CoV-2. Researchers looking at New York City health cases split up COVID-19 patients into clusters based on distinguishing features, including obesity, to form a "decision tree" for statistical analysis . PubMed Central Sometimes coronaviruses that infect animals can evolve and make people sick and become a new human coronavirus. Cite this article. The importance of distinguishing COVID-19 from more common respiratory Alharbi, N. K. et al. Structure 28, 12181224.e1214 (2020). 2c)20,21. Immunol 11, 1673 (2020). These modifications (indicated in Table1 and in the discussion of individual vaccines below) include two proline mutations in S2 (K986P and V987P) at the junction between two alpha helices in the pre-fusion form to avert their fusogenic conformational switch into a long alpha helix in the post-fusion form, and mutations that abolish furin cleavage between S1 and S2 to maintain the pre-fusion trimer and to prevent shedding of S118 (Fig. 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. Correspondence to Z., Jacobsen, S. & Ndeupen, S. Future considerations for the mRNA-lipid nanoparticle vaccine platform. Comparison of Clinical Features of COVID-19 vs Seasonal - JAMA FEMA helps the public distinguish between rumors and facts regarding the response to the Coronavirus (COVID-19) pandemic. 100, 309354 (2018). Science 369, 956 (2020). Results from a phase 1 clinical trial with the Curevac vaccine had indeed already shown relatively low titers of neutralizing antibodies induced by the dose used in the phase 3 clinical trial56,59. & Edwards, K. M.) 7583.e72 (Elsevier, 2018). N. Engl. distinguishing feature of COVID-19 compared with other infective pneumonias and its association with disease severity Meera Mehta ,1 Hakim Ghani ,1 Felix Chua,2,3 Adrian Draper,4 Sam Calmonson,1 Meghna Prabhakar,1 Rijul Shah,1 Alessio Navarra,1 Tejal Vaghela,1 Andrew Barlow,1 Rama Vancheeswaran1 On average a coronavirus particle has 74 surface spikes. Dicks, M. D. J. et al. b Schematic of the process using an additional N-terminal leader sequence (signal peptide and propeptide of tPA), as used in the vaccine of Oxford-Astra Zeneca, based on reference. The two mRNA vaccines in current widespread application (BioNTech-Pfizer and Moderna) (Table1) are technologically very similar. Immunity 54, 12761289.e1276 (2021). J. Med. Mumbai Sees Two Covid-19 Cases, No Death; Active Tally Now 11. Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data. Control. The coronavirus disease 2019 (COVID-19) pandemic is currently spreading worldwide and contributing to widespread mortality. The potency of these antibodies depends on high-affinity interactions with specific parts of the complex three-dimensional structure of the spike in a native conformation10,11. Different from SARS-CoV and MERS-CoV in genetics and epidemiology, SARS-CoV-2 is a novel -coronavirus [ 6, 7 ]. 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. According to research published in Rhinology, COVID-19 can cause a loss of taste and smell even without congestion.