{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T21:30:06Z","timestamp":1775856606651,"version":"3.50.1"},"reference-count":91,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T00:00:00Z","timestamp":1642032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>The global response to Coronavirus Disease 2019 (COVID-19) is now facing new challenges such as vaccine inequity and the emergence of SARS-CoV-2 variants of concern (VOCs). Preclinical models of disease, in particular animal models, are essential to investigate VOC pathogenesis, vaccine correlates of protection and postexposure therapies. Here, we provide an update from the World Health Organization (WHO) COVID-19 modeling expert group (WHO-COM) assembled by WHO, regarding advances in preclinical models. In particular, we discuss how animal model research is playing a key role to evaluate VOC virulence, transmission and immune escape, and how animal models are being refined to recapitulate COVID-19 demographic variables such as comorbidities and age.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010161","type":"journal-article","created":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T18:29:05Z","timestamp":1642098545000},"page":"e1010161","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":81,"title":["Advances and gaps in SARS-CoV-2 infection models"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7725-2586","authenticated-orcid":true,"given":"C\u00e9sar","family":"Mu\u00f1oz-Fontela","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6666-7770","authenticated-orcid":true,"given":"Lina","family":"Widerspick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4008-503X","authenticated-orcid":true,"given":"Randy A.","family":"Albrecht","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Beer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miles W.","family":"Carroll","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9763-7758","authenticated-orcid":true,"given":"Emmie","family":"de Wit","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8791-3165","authenticated-orcid":true,"given":"Michael S.","family":"Diamond","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3277-6199","authenticated-orcid":true,"given":"William E.","family":"Dowling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon G. P.","family":"Funnell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6551-1827","authenticated-orcid":true,"given":"Adolfo","family":"Garc\u00eda-Sastre","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nora M.","family":"Gerhards","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2052-5993","authenticated-orcid":true,"given":"Rineke","family":"de Jong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2288-3196","authenticated-orcid":true,"given":"Vincent J.","family":"Munster","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0033-7514","authenticated-orcid":true,"given":"Johan","family":"Neyts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanley","family":"Perlman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0076-9023","authenticated-orcid":true,"given":"Douglas S.","family":"Reed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7308-5672","authenticated-orcid":true,"given":"Juergen A.","family":"Richt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ximena","family":"Riveros-Balta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1710-6974","authenticated-orcid":true,"given":"Chad J.","family":"Roy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5315-3882","authenticated-orcid":true,"given":"Francisco J.","family":"Salguero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3156-3132","authenticated-orcid":true,"given":"Michael","family":"Schotsaert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2264-3029","authenticated-orcid":true,"given":"Lauren M.","family":"Schwartz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Seder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1539-7261","authenticated-orcid":true,"given":"Joaquim","family":"Segal\u00e9s","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7326-3210","authenticated-orcid":true,"given":"Seshadri S.","family":"Vasan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Mar\u00eda","family":"Henao-Restrepo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5127-4659","authenticated-orcid":true,"given":"Dan H.","family":"Barouch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,1,13]]},"reference":[{"key":"ppat.1010161.ref001","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/s41586-020-2787-6","article-title":"Animal models for COVID-19","volume":"586","author":"C Munoz-Fontela","year":"2020","journal-title":"Nature"},{"key":"ppat.1010161.ref002","first-page":"1","article-title":"Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques","author":"NB Mercado","year":"2020","journal-title":"Nature"},{"key":"ppat.1010161.ref003","article-title":"ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques","author":"N van Doremalen","year":"2020","journal-title":"bioRxiv"},{"key":"ppat.1010161.ref004","first-page":"NEJMoa2024671","article-title":"Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates","author":"KS Corbett","year":"2020","journal-title":"N Engl J Med"},{"key":"ppat.1010161.ref005","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/s41586-021-03275-y","article-title":"BNT162b vaccines protect rhesus macaques from SARS-CoV-2","volume":"592","author":"AB Vogel","year":"2021","journal-title":"Nature."},{"key":"ppat.1010161.ref006","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1056\/NEJMsr2105280","article-title":"SARS-CoV-2 Variants and Vaccines","volume":"385","author":"PR Krause","year":"2021","journal-title":"N Engl J Med"},{"key":"ppat.1010161.ref007","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1038\/s41564-020-0770-5","article-title":"A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology","volume":"5","author":"A Rambaut","year":"2020","journal-title":"Nat Microbiol."},{"key":"ppat.1010161.ref008","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1080\/22221751.2021.1943539","article-title":"Prior aerosol infection with lineage A SARS-CoV-2 variant protects hamsters from disease, but not reinfection with B.1.351 SARS-CoV-2 variant.","volume":"10","author":"CK Yinda","year":"2021","journal-title":"Emerg Microbes Infect"},{"key":"ppat.1010161.ref009","doi-asserted-by":"crossref","first-page":"103403","DOI":"10.1016\/j.ebiom.2021.103403","article-title":"Comparing infectivity and virulence of emerging SARS-CoV-2 variants in Syrian hamsters","volume":"68","author":"R Abdelnabi","year":"2021","journal-title":"EBioMedicine"},{"key":"ppat.1010161.ref010","doi-asserted-by":"crossref","first-page":"e0050721","DOI":"10.1128\/mSphere.00507-21","article-title":"SARS-CoV-2 B.1.1.7 Infection of Syrian Hamster Does Not Cause More Severe Disease, and Naturally Acquired Immunity Confers Protection","author":"IA Nu\u00f1ez","year":"2021","journal-title":"mSphere"},{"key":"ppat.1010161.ref011","doi-asserted-by":"crossref","first-page":"109452","DOI":"10.1016\/j.celrep.2021.109452","article-title":"An intranasal vaccine durably protects against SARS-CoV-2 variants in mice","volume":"36","author":"AO Hassan","year":"2021","journal-title":"Cell Rep."},{"key":"ppat.1010161.ref012","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/s41586-021-03732-8","article-title":"Protective efficacy of Ad26.COV2.S against SARS-CoV-2 B.1.351 in macaques","volume":"596","author":"J Yu","year":"2021","journal-title":"Nature."},{"key":"ppat.1010161.ref013","article-title":"Immunity elicited by natural infection or Ad26.COV2.S vaccination protects hamsters against SARS-CoV-2 variants of concern","author":"LH Tostanoski","year":"2021","journal-title":"Sci Transl Med."},{"key":"ppat.1010161.ref014","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.3390\/v13091773","article-title":"SARS-CoV-2 Delta Variant Pathogenesis and Host Response in Syrian Hamsters","volume":"13","author":"S Mohandas","year":"2021","journal-title":"Viruses"},{"key":"ppat.1010161.ref015","doi-asserted-by":"crossref","first-page":"eabj2641","DOI":"10.1126\/scitranslmed.abj2641","article-title":"Prior infection with SARS-CoV-2 WA1\/2020 partially protects rhesus macaques against reinfection with B.1.1.7 and B.1.351 variants","volume":"13","author":"A Chandrashekar","year":"2021","journal-title":"Sci Transl Med"},{"key":"ppat.1010161.ref016","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1080\/22221751.2021.1913974","article-title":"Protection against reinfection with D614- or G614-SARS-CoV-2 isolates in golden Syrian hamster","volume":"10","author":"M Brustolin","year":"2021","journal-title":"Emerg Microbes Infect"},{"key":"ppat.1010161.ref017","doi-asserted-by":"crossref","first-page":"2322","DOI":"10.1080\/22221751.2020.1833687","article-title":"SARS-CoV-2 infection, disease and transmission in domestic cats","volume":"9","author":"NN Gaudreault","year":"2020","journal-title":"Emerg Microbes Infect"},{"key":"ppat.1010161.ref018","article-title":"The impact of SARS-CoV-2 vaccination on Alpha & Delta variant transmission","author":"DW Eyre","year":"2021","journal-title":"medRxiv"},{"key":"ppat.1010161.ref019","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s41541-021-00315-6","article-title":"ChAdOx1 nCoV-19 (AZD1222) vaccine candidate significantly reduces SARS-CoV-2 shedding in ferrets","volume":"6","author":"GA Marsh","year":"2021","journal-title":"NPJ Vaccines"},{"key":"ppat.1010161.ref020","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abh0755","article-title":"Intranasal ChAdOx1 nCoV-19\/AZD1222 vaccination reduces viral shedding after SARS-CoV-2 D614G challenge in preclinical models","volume":"13","author":"N van Doremalen","year":"2021","journal-title":"Sci Transl Med"},{"key":"ppat.1010161.ref021","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/s41586-021-03361-1","article-title":"SARS-CoV-2 spike D614G change enhances replication and transmission","volume":"592","author":"B Zhou","year":"2021","journal-title":"Nature"},{"key":"ppat.1010161.ref022","article-title":"Enhanced fitness of SARS-CoV-2 variant of concern B.1.1.7, but not B.1.351, in animal models","author":"L Ulrich","year":"2021","journal-title":"bioRxiv"},{"key":"ppat.1010161.ref023","article-title":"Increased aerosol transmission for B.1.1.7 (alpha variant) over lineage A variant of SARS-CoV-2","author":"JR Port","year":"2021","journal-title":"bioRxiv"},{"key":"ppat.1010161.ref024","article-title":"Infection and transmission of SARS-CoV-2 and its alpha variant in pregnant white-tailed deer","author":"K Cool","year":"2021","journal-title":"bioRxiv"},{"key":"ppat.1010161.ref025","article-title":"The N501Y mutation in SARS-CoV-2 spike leads to morbidity in obese and aged mice and is neutralized by convalescent and post-vaccination human sera","author":"R Rathnasinghe","year":"2021","journal-title":"medRxiv"},{"key":"ppat.1010161.ref026","article-title":"SARS-CoV-2 B.1.351 (beta) variant shows enhanced infectivity in K18-hACE2 transgenic mice and expanded tropism to wildtype mice compared to B.1 variant","author":"F Tarr\u00e9s-Freixas","year":"2021","journal-title":"bioRxiv"},{"key":"ppat.1010161.ref027","article-title":"The B1.351 and P.1 variants extend SARS-CoV-2 host range to mice","author":"X Montagutelli","year":"2021","journal-title":"bioRxiv"},{"key":"ppat.1010161.ref028","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1016\/j.immuni.2021.06.003","article-title":"Analysis of SARS-CoV-2 variant mutations reveals neutralization escape mechanisms and the ability to use ACE2 receptors from additional species","volume":"54","author":"R Wang","year":"2021","journal-title":"Immunity"},{"key":"ppat.1010161.ref029","doi-asserted-by":"crossref","first-page":"104878","DOI":"10.1016\/j.antiviral.2020.104878","article-title":"In vitro evaluation of antiviral activity of single and combined repurposable drugs against SARS-CoV-2","volume":"181","author":"A Pizzorno","year":"2020","journal-title":"Antiviral Res"},{"key":"ppat.1010161.ref030","doi-asserted-by":"crossref","first-page":"4253","DOI":"10.1038\/s41467-020-17907-w","article-title":"Emerging preclinical evidence does not support broad use of hydroxychloroquine in COVID-19 patients","volume":"11","author":"SGP Funnell","year":"2020","journal-title":"Nat Commun"},{"key":"ppat.1010161.ref031","article-title":"Subtle differences in the pathogenicity of SARS-CoV-2 variants of concern B.1.1.7 and B.1.351 in rhesus macaques","author":"VJ Munster","year":"2021","journal-title":"bioRxiv"},{"key":"ppat.1010161.ref032","article-title":"UK B.1.1.7 variant exhibits increased respiratory replication and shedding in nonhuman primates","author":"K Rosenke","year":"2021","journal-title":"bioRxiv"},{"key":"ppat.1010161.ref033","article-title":"Evolution of enhanced innate immune evasion by the SARS-CoV-2 B.1.1.7 UK variant","author":"LG Thorne","year":"2021","journal-title":"bioRxiv"},{"key":"ppat.1010161.ref034","article-title":"SARS-CoV-2 variants of concern have acquired mutations associated with an increased spike cleavage","author":"A Escalera","year":"2021","journal-title":"bioRxiv"},{"key":"ppat.1010161.ref035","article-title":"The SARS-CoV-2 variants associated with infections in India, B.1.617, show enhanced spike cleavage by furin","author":"TP Peacock","year":"2021","journal-title":"bioRxiv"},{"key":"ppat.1010161.ref036","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/s41586-020-2294-9","article-title":"Rapid reconstruction of SARS-CoV-2 using a synthetic genomics platform","volume":"582","author":"T Thi Nhu Thao","year":"2020","journal-title":"Nature"},{"key":"ppat.1010161.ref037","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1093\/oxfordjournals.aje.a120955","article-title":"Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine","volume":"89","author":"HW Kim","year":"1969","journal-title":"Am J Epidemiol"},{"key":"ppat.1010161.ref038","doi-asserted-by":"crossref","first-page":"161","DOI":"10.3109\/inf.1970.2.issue-3.02","article-title":"Atypical measles after vaccination with killed vaccine","volume":"2","author":"T R\u00f8d","year":"1970","journal-title":"Scand J Infect Dis"},{"key":"ppat.1010161.ref039","first-page":"1","article-title":"Dengue virus: epidemiology, biology, and disease aetiology","author":"SK Roy","year":"2021","journal-title":"Can J Microbiol"},{"key":"ppat.1010161.ref040","article-title":"Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry","volume":"94","author":"Y Wan","year":"2020","journal-title":"J Virol"},{"key":"ppat.1010161.ref041","doi-asserted-by":"crossref","first-page":"12201","DOI":"10.1128\/JVI.06048-11","article-title":"A double-inactivated severe acute respiratory syndrome coronavirus vaccine provides incomplete protection in mice and induces increased eosinophilic proinflammatory pulmonary response upon challenge","volume":"85","author":"M Bolles","year":"2011","journal-title":"J Virol"},{"key":"ppat.1010161.ref042","doi-asserted-by":"crossref","first-page":"e35421","DOI":"10.1371\/journal.pone.0035421","article-title":"Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. Poehlmann S, editor","volume":"7","author":"C-T Tseng","year":"2012","journal-title":"PLoS ONE"},{"key":"ppat.1010161.ref043","doi-asserted-by":"crossref","first-page":"12672","DOI":"10.1128\/JVI.78.22.12672-12676.2004","article-title":"Immunization with modified vaccinia virus Ankara-based recombinant vaccine against severe acute respiratory syndrome is associated with enhanced hepatitis in ferrets","volume":"78","author":"H Weingartl","year":"2004","journal-title":"J Virol"},{"key":"ppat.1010161.ref044","doi-asserted-by":"crossref","first-page":"3053","DOI":"10.1016\/j.vaccine.2021.01.055","article-title":"Vaccine-associated enhanced disease: Case definition and guidelines for data collection, analysis, and presentation of immunization safety data","volume":"39","author":"FM Munoz","year":"2021","journal-title":"Vaccine"},{"key":"ppat.1010161.ref045","doi-asserted-by":"crossref","first-page":"eabg7996","DOI":"10.1126\/sciadv.abg7996","article-title":"Immunological and pathological outcomes of SARS-CoV-2 challenge following formalin-inactivated vaccine in ferrets and rhesus macaques","volume":"7","author":"KR Bewley","year":"2021","journal-title":"Sci Adv"},{"key":"ppat.1010161.ref046","doi-asserted-by":"crossref","first-page":"4048","DOI":"10.1038\/s41467-021-24339-7","article-title":"CVnCoV and CV2CoV protect human ACE2 transgenic mice from ancestral B BavPat1 and emerging B.1.351 SARS-CoV-2","volume":"12","author":"D Hoffmann","year":"2021","journal-title":"Nat Commun"},{"key":"ppat.1010161.ref047","doi-asserted-by":"crossref","first-page":"689065","DOI":"10.3389\/fimmu.2021.689065","article-title":"Generation and Effect Testing of a SARS-CoV-2 RBD-Targeted Polyclonal Therapeutic Antibody Based on a 2-D Airway Organoid Screening System","volume":"12","author":"Y He","year":"2021","journal-title":"Front Immunol Frontiers"},{"key":"ppat.1010161.ref048","doi-asserted-by":"crossref","first-page":"e1009704","DOI":"10.1371\/journal.ppat.1009704","article-title":"Structure-guided antibody cocktail for prevention and treatment of COVID-19","volume":"17","author":"S-C Su","year":"2021","journal-title":"PLoS Pathog"},{"key":"ppat.1010161.ref049","doi-asserted-by":"crossref","first-page":"6097","DOI":"10.1038\/s41467-021-26354-0","article-title":"COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models","volume":"12","author":"P Maisonnasse","year":"2021","journal-title":"Nat Commun"},{"key":"ppat.1010161.ref050","doi-asserted-by":"crossref","first-page":"109814","DOI":"10.1016\/j.celrep.2021.109814","article-title":"A highly potent antibody effective against SARS-CoV-2 variants of concern","volume":"37","author":"C Fenwick","year":"2021","journal-title":"Cell Rep"},{"key":"ppat.1010161.ref051","doi-asserted-by":"crossref","first-page":"e1009542","DOI":"10.1371\/journal.ppat.1009542","article-title":"Nasal delivery of single-domain antibody improves symptoms of SARS-CoV-2 infection in an animal model","volume":"17","author":"K Haga","year":"2021","journal-title":"PLoS Pathog"},{"key":"ppat.1010161.ref052","doi-asserted-by":"crossref","first-page":"5469","DOI":"10.1038\/s41467-021-25480-z","article-title":"A potent SARS-CoV-2 neutralising nanobody shows therapeutic efficacy in the Syrian golden hamster model of COVID-19","volume":"12","author":"J Huo","year":"2021","journal-title":"Nat Commun."},{"key":"ppat.1010161.ref053","doi-asserted-by":"crossref","first-page":"eabj2901","DOI":"10.1126\/sciimmunol.abj2901","article-title":"Early cross-coronavirus reactive signatures of humoral immunity against COVID-19","volume":"6","author":"P Kaplonek","year":"2021","journal-title":"Sci Immunol"},{"key":"ppat.1010161.ref054","first-page":"1","article-title":"Fc-engineered antibody therapeutics with improved anti-SARS-CoV-2 efficacy","author":"R Yamin","year":"2021","journal-title":"Nature"},{"key":"ppat.1010161.ref055","first-page":"1","article-title":"Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2","author":"BN Williamson","year":"2020","journal-title":"Nature"},{"key":"ppat.1010161.ref056","doi-asserted-by":"crossref","first-page":"26955","DOI":"10.1073\/pnas.2014441117","article-title":"Favipiravir at high doses has potent antiviral activity in SARS-CoV-2-infected hamsters, whereas hydroxychloroquine lacks activity","volume":"117","author":"SJF Kaptein","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1010161.ref057","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-021-22580-8","article-title":"Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model","volume":"12","author":"K Rosenke","year":"2021","journal-title":"Nat Commun"},{"key":"ppat.1010161.ref058","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41564-020-00835-2","article-title":"Therapeutically administered ribonucleoside analogue MK-4482\/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets","volume":"6","author":"RM Cox","year":"2021","journal-title":"Nat Microbiol"},{"key":"ppat.1010161.ref059","doi-asserted-by":"crossref","first-page":"6055","DOI":"10.1038\/s41467-021-26239-2","article-title":"Preclinical characterization of an intravenous coronavirus 3CL protease inhibitor for the potential treatment of COVID19","volume":"12","author":"B Boras","year":"2021","journal-title":"Nat Commun."},{"key":"ppat.1010161.ref060","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abf8396","article-title":"COVID-19-related anosmia is associated with viral persistence and inflammation in human olfactory epithelium and brain infection in hamsters","volume":"13","author":"GD de Melo","year":"2021","journal-title":"Sci Transl Med"},{"key":"ppat.1010161.ref061","doi-asserted-by":"crossref","first-page":"639","DOI":"10.3390\/v13040639","article-title":"Vascular Inflammation Is Associated with Loss of Aquaporin 1 Expression on Endothelial Cells and Increased Fluid Leakage in SARS-CoV-2 Infected Golden Syrian Hamsters.","volume":"13","author":"L Allnoch","year":"2021","journal-title":"Viruses"},{"key":"ppat.1010161.ref062","doi-asserted-by":"crossref","first-page":"640842","DOI":"10.3389\/fimmu.2021.640842","article-title":"Vasculitis and Neutrophil Extracellular Traps in Lungs of Golden Syrian Hamsters With SARS-CoV-2","volume":"12","author":"K Becker","year":"2021","journal-title":"Front Immunol"},{"key":"ppat.1010161.ref063","doi-asserted-by":"crossref","first-page":"e0097421","DOI":"10.1128\/mBio.00974-21","article-title":"Sex Differences in Lung Imaging and SARS-CoV-2 Antibody Responses in a COVID-19 Golden Syrian Hamster Model","volume":"12","author":"S Dhakal","year":"2021","journal-title":"mBio"},{"key":"ppat.1010161.ref064","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/s41392-021-00552-0","article-title":"Gender associates with both susceptibility to infection and pathogenesis of SARS-CoV-2 in Syrian hamster","volume":"6","author":"L Yuan","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"ppat.1010161.ref065","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/s41586-020-2700-3","article-title":"Sex differences in immune responses that underlie COVID-19 disease outcomes","volume":"588","author":"T Takahashi","year":"2020","journal-title":"Nature"},{"key":"ppat.1010161.ref066","doi-asserted-by":"crossref","first-page":"779","DOI":"10.3390\/v12070779","article-title":"Age-Dependent Progression of SARS-CoV-2 Infection in Syrian Hamsters","volume":"12","author":"N Osterrieder","year":"2020","journal-title":"Viruses."},{"key":"ppat.1010161.ref067","doi-asserted-by":"crossref","first-page":"824","DOI":"10.3390\/pathogens10070824","article-title":"Predictive Value of Precision-Cut Lung Slices for the Susceptibility of Three Animal Species for SARS-CoV-2 and Validation in a Refined Hamster Model","volume":"10","author":"NM Gerhards","year":"2021","journal-title":"Pathogens"},{"key":"ppat.1010161.ref068","doi-asserted-by":"crossref","first-page":"16587","DOI":"10.1073\/pnas.2009799117","article-title":"Syrian hamsters as a small animal model for SARS-CoV-2 infection and countermeasure development","volume":"117","author":"M Imai","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1010161.ref069","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1038\/s41467-021-21389-9","article-title":"Comparison of rhesus and cynomolgus macaques as an infection model for COVID-19","volume":"12","author":"FJ Salguero","year":"2021","journal-title":"Nat Commun"},{"key":"ppat.1010161.ref070","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.virol.2020.12.013","article-title":"Neutralizing antibody-dependent and -independent immune responses against SARS-CoV-2 in cynomolgus macaques","volume":"554","author":"H Ishigaki","year":"2021","journal-title":"Virology"},{"key":"ppat.1010161.ref071","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1126\/science.abb7314","article-title":"Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model","volume":"368","author":"B Rockx","year":"2020","journal-title":"Science"},{"key":"ppat.1010161.ref072","first-page":"265","article-title":"Respiratory disease in rhesus macaques inoculated with SARS-CoV-2","volume":"579","author":"VJ Munster","year":"2020","journal-title":"Nature"},{"key":"ppat.1010161.ref073","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1016\/j.cell.2020.09.050","article-title":"A Mouse-Adapted SARS-CoV-2 Induces Acute Lung Injury and Mortality in Standard Laboratory Mice","volume":"183","author":"SR Leist","year":"2020","journal-title":"Cell"},{"key":"ppat.1010161.ref074","doi-asserted-by":"crossref","first-page":"103381","DOI":"10.1016\/j.ebiom.2021.103381","article-title":"Q493K and Q498H substitutions in Spike promote adaptation of SARS-CoV-2 in mice.","volume":"67","author":"K Huang","year":"2021","journal-title":"EBioMedicine"},{"key":"ppat.1010161.ref075","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1038\/s41590-020-0778-2","article-title":"SARS-CoV-2 infection of human ACE2-transgenic mice causes severe lung inflammation and impaired function","volume":"21","author":"ES Winkler","year":"2020","journal-title":"Nat Immunol"},{"key":"ppat.1010161.ref076","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/s41586-020-2943-z","article-title":"COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice","volume":"589","author":"J Zheng","year":"2021","journal-title":"Nature"},{"key":"ppat.1010161.ref077","doi-asserted-by":"crossref","first-page":"e1000849","DOI":"10.1371\/journal.ppat.1000849","article-title":"SARS-CoV pathogenesis is regulated by a STAT1 dependent but a type I, II and III interferon receptor independent mechanism","volume":"6","author":"MB Frieman","year":"2010","journal-title":"PLoS Pathog"},{"key":"ppat.1010161.ref078","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1084\/jem.20150632","article-title":"Critical role of phospholipase A2 group IID in age-related susceptibility to severe acute respiratory syndrome-CoV infection","volume":"212","author":"R Vijay","year":"2015","journal-title":"J Exp Med"},{"key":"ppat.1010161.ref079","first-page":"571416","article-title":"Aging, Immunity, and COVID-19: How Age Influences the Host Immune Response to Coronavirus Infections? Front Physiol","volume":"11","author":"V Bajaj","year":"2020","journal-title":"Frontiers"},{"key":"ppat.1010161.ref080","article-title":"Age-dependent pathogenic characteristics of SARS-CoV-2 infection in ferrets","author":"Y-I Kim","year":"2021","journal-title":"Res Sq"},{"key":"ppat.1010161.ref081","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1016\/j.chom.2020.04.009","article-title":"Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure","volume":"27","author":"EJ Giamarellos-Bourboulis","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ppat.1010161.ref082","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1016\/j.cell.2020.09.038","article-title":"Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity","volume":"183","author":"C Rydyznski Moderbacher","year":"2020","journal-title":"Cell"},{"key":"ppat.1010161.ref083","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/s41564-020-00841-4","article-title":"Responses to acute infection with SARS-CoV-2 in the lungs of rhesus macaques, baboons and marmosets","volume":"6","author":"DK Singh","year":"2021","journal-title":"Nat Microbiol"},{"key":"ppat.1010161.ref084","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.ajpath.2020.10.016","article-title":"Acute Respiratory Distress in Aged, SARS-CoV-2-Infected African Green Monkeys but Not Rhesus Macaques","volume":"191","author":"RV Blair","year":"2021","journal-title":"Am J Pathol"},{"key":"ppat.1010161.ref085","article-title":"Age-related differences in immune dynamics during SARS-CoV-2 infection in rhesus macaques","author":"E Speranza","year":"2021","journal-title":"bioRxiv"},{"key":"ppat.1010161.ref086","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1002\/ame2.12155","article-title":"SARS-CoV-2 infection aggravates chronic comorbidities of cardiovascular diseases and diabetes in mice","volume":"4","author":"Y Ma","year":"2021","journal-title":"Animal Model Exp Med"},{"key":"ppat.1010161.ref087","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/s41569-020-0413-9","article-title":"COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives","volume":"17","author":"M Nishiga","year":"2020","journal-title":"Nat Rev Cardiol"},{"key":"ppat.1010161.ref088","article-title":"Western diet increases COVID-19 disease severity in the Syrian hamster","author":"JR Port","year":"2021","journal-title":"bioRxiv"},{"key":"ppat.1010161.ref089","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s41541-021-00292-w","article-title":"SARS-CoV-2 vaccines strategies: a comprehensive review of phase 3 candidates","volume":"6","author":"NC Kyriakidis","year":"2021","journal-title":"NPJ Vaccines"},{"key":"ppat.1010161.ref090","doi-asserted-by":"crossref","first-page":"n723","DOI":"10.1136\/bmj.n723","article-title":"Covid vaccine could be rolled out to children by autumn","volume":"372","author":"E. Mahase","year":"2021","journal-title":"BMJ"},{"key":"ppat.1010161.ref091","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1038\/s41586-020-03041-6","article-title":"Correlates of protection against SARS-CoV-2 in rhesus macaques","volume":"590","author":"K McMahan","year":"2021","journal-title":"Nature."}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1010161","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,22]],"date-time":"2023-01-22T21:52:46Z","timestamp":1674424366000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1010161"}},"subtitle":[],"editor":[{"given":"Helen M.","family":"Lazear","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2022,1,13]]},"references-count":91,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1,13]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1010161","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,13]]}}}