Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant B.1.1.7 causes a more transmissible and apparently more severe disease. We report its early introduction from Europe to South America from a traveler who arrived in Uruguay from the United Kingdom, even before B.1.1.7 was recognized as a variant of concern. This highlights the risk of introduction of SARS-CoV-2 variants despite strict contingency protocols and underscores the need of improving real-time surveillance worldwide.ANII: POS_NAC_2018_1_15149

Antelo, Virginia

Costábile Cristech, Alicia

Ferrés Cáceres, Ignacio

Galiana, Antonio

García, Rosario

Iraola, Gregorio

Moratorio, Gonzalo

Moreno Karlen, María del Pilar

Perbolianachis Duarte, Paula

Pereira Gómez, Marianoel

Pi, Beatriz

Salazar González, María Cecilia

Simón, Diego

English

LAReferencia - Red Federada de Repositorios Institucionales de Publicaciones Científicas Latinoamericanas

CASE REPORTpublished: 28 May 2021doi: 10.3389/fviro.2021.685618Frontiers in Virology | www.frontiersin.org 1 May 2021 | Volume 1 | Article 685618Edited by:Jacqueline Weyer,National Institute of CommunicableDiseases (NICD), South AfricaReviewed by:Katherine Laiton Donato,Instituto Nacional de Salud, ColombiaGiuseppe Oliveto,Sapienza University of Rome, Italy*Correspondence:Pilar Morenopmoreno@pasteur.edu.uyGonzalo Moratoriomoratorio@pasteur.edu.uyGregorio Iraolagiraola@pasteur.edu.uy†These authors have contributedequally to this workSpecialty section:This article was submitted toEmerging and Reemerging Viruses,a section of the journalFrontiers in VirologyReceived: 25 March 2021Accepted: 30 April 2021Published: 28 May 2021Citation:Salazar C, Costabile A, Ferrés I,Perbolianachis P, Pereira-Gómez M,Simón D, Galiana A, Pi B, Antelo V,García R, Moreno P, Moratorio G andIraola G (2021) Case Report: EarlyTranscontinental Import ofSARS-CoV-2 Variant of Concern202012/01 (B.1.1.7) From Europe toUruguay. Front. Virol. 1:685618.doi: 10.3389/fviro.2021.685618Case Report: Early TranscontinentalImport of SARS-CoV-2 Variant ofConcern 202012/01 (B.1.1.7) FromEurope to UruguayCecilia Salazar 1,2†, Alicia Costabile 2,3,4,5†, Ignacio Ferrés 1,2, Paula Perbolianachis 4,5,Marianoel Pereira-Gómez 4,5, Diego Simón 4,5, Antonio Galiana 6,7, Beatriz Pi 7,Virginia Antelo 7, Rosario García 7, Pilar Moreno 2,4,5*, Gonzalo Moratorio 2,4,5* andGregorio Iraola 1,2,8*1 Laboratorio de Genómica Microbiana, Institut Pasteur de Montevideo, Montevideo, Uruguay, 2Centro de Innovación enVigilancia Epidemiológica (CiVE), Institut Pasteur de Montevideo, Montevideo, Uruguay, 3 Sección Bioquímica y BiologíaMolecular, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay, 4 Laboratorio de Evolución Experimentalde Virus, Institut Pasteur de Montevideo, Montevideo, Uruguay, 5 Laboratorio de Virología Molecular, Facultad de Ciencias,Universidad de la República, Montevideo, Uruguay, 6Hospital Maciel, Montevideo, Uruguay, 7 Asistencial Médica deMaldonado, Maldonado, Uruguay, 8Wellcome Sanger Institute, Hinxton, United KingdomSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant B.1.1.7 causes amore transmissible and apparently more severe disease. We report its early introductionfrom Europe to South America from a traveler who arrived in Uruguay from theUnited Kingdom, even before B.1.1.7 was recognized as a variant of concern. Thishighlights the risk of introduction of SARS-CoV-2 variants despite strict contingencyprotocols and underscores the need of improving real-time surveillance worldwide.Keywords: COVID-19, SARS-CoV-2, B.1.1.7 variant, South America, transcontinental, Uruguay, VOCINTRODUCTIONOn December 14, 2020, the United Kingdom (UK) reported a severe acute respiratory syndromecoronavirus 2 (SARS-CoV-2) variant of concern (VOC), currently known as VOC 202012/01,20I/501Y.V1 or lineage B.1.1.7. The emergence of this variant has been estimated to September2020 and then quickly become themain circulating SARS-CoV-2 variant in England (1). The highertransmission capacity of this variant and its apparent capacity to cause a more severe illness (2) arerising concerns internationally (3), triggering specific efforts to contain its spread.CASE DESCRIPTIONOn December 15, 2020, a 27-year-old male Uruguayan citizen who has been residing in the UKduring the past 18 months, flew from the UK to Uruguay (Figure 1A). The trip consisted in adirect flight from London (UK) to Madrid (Spain), where he remained in transit (not leavingthe airport) during 2 h to subsequently take a connection flight to Montevideo (Uruguay). TheCOVID-19 contingency protocol in Uruguay requires a negative SARS-CoV-2 RT-qPCR test upto 72 h before arrival to the country, which had been performed and resulted negative in theUK on December 12, 2020. Also, as part of the national protocol, the patient was isolated at hisarrival to fulfill a preventive 14-day quarantine. Five days after arrival, on December 20, 2020,the patient developed symptoms compatible with COVID-19 such as fever, cough, headache, andmyalgia. Then, on December 22, 2020, the patient tested positive for SARS-CoV-2 by RT-qPCRSalazar et al. Transcontinental B.1.1.7 Import to UruguayFIGURE 1 | Import of the SARS-CoV-2 variant B.1.1.7 into South America. (A) Timeline of main events related to the B.1.1.7 case imported from the UK to Uruguayon December 20, 2020. (B) Status of B.1.1.7 distribution in South American countries. (C) Elapsed time from B.1.1.7 introduction and report in South America.Horizontal bars span from the date of introduction (when known) to the date of official report of B.1.1.7 presence in each country.performed in a private lab. Two days after, on December 24,2020, the patient developed dyspnea requiring of hospitalization.Clinical evaluation revealed lympophenia, azotemia and elevatedlevels of C-reactive protein. Chest X-ray showed diffuseinterstitial infiltrate with slight opacity erasing the rightcostophrenic angle. These observations were compatible withCOVID-19 pneumonia and a probable bacterial secondaryinfection, so thromboprophylaxis was started together withFrontiers in Virology | www.frontiersin.org 2 May 2021 | Volume 1 | Article 685618Salazar et al. Transcontinental B.1.1.7 Import to Uruguaycorticosteroids, ampicillin-sulbactam and clarithromycin. Thepatient remained admitted for 6 days in a moderate care areawith excellent evolution. On December 30, 2020, the patientrecovered and was remitted from hospital with absence of anyclinical signs of COVID-19. After that, the patient remainedin quarantine at his home co-inhabiting but isolated from hisfamily (five people ranging from 15 to 85 years old). Due to aquarantine protocol misinterpretation, the family was in contactwith the patient during 48 h, on January 2, 2021 so all they weresubsequently quarantined for 7 days being asymptomatic duringthis period. On January 9, 2021, patient’s family members weretested for SARS-CoV-2 and resulted negative. A retrospectiveepidemiological investigation evidenced two additional contacts.First, the day before the patient’s pre-trip test was performed inthe UK, he was in contact during 1 h and without using facemasks with a person who developed COVID-19 symptoms onDecember 20, 2020, and then tested positive in the UK. Second, afriend took the patient at his arrival from the airport to his homeinMontevideo in a particular car. Once the patient was diagnosedwith COVID-19, his friend was quarantined for 14 days beingasymptomatic and testing negative at the end of this period.Given the potential epidemiological relevance of this case,a retrospective genomic and molecular analysis was performedon the patient’s positive nasopharyngeal swab sample collectedon December 22, 2020. First, we used the “COVID-19 RT-PCR Real TM Fast-HEX/Cy5” (Institut Pasteur de Montevideo,Universidad de la República, ATGen) to re-confirm the presenceof SARS-CoV-2 in this sample, that resulted positive again witha cycle threshold of 30. Then, the sample was submitted to theSARS-CoV-2 genome sequencing pipeline at the Institut Pasteurde Montevideo, using the ARCTIC Network protocol for theMinION platform (4), as previously implemented (5). Due todegradation of the original sample, amplification of the wholegenome was not achieved. However, mapping of resulting readsagainst the reference SARS-CoV-2 genome Wuhan-1 (GISAIDaccession no. EPI_ISL_302124) revealed specific diagnosticmutations of lineage B.1.1.7 in the spike gene, including P681H(C23604A), T716I (C23709T), S982A (T24506G), and D1118H(G24914C). To confirm this, we performed one in-house and onepreviously published (6) RT-qPCR assay specifically designed forthe detection and differentiation of VOC B.1.1.7, B.1.1.351 andP.1. These assays target the ORF1a 13675-3677 and spike 169-70 deletions, but using different primers and probes. In bothcases, results were consistent with the presence of the B.1.1.7lineage. Together, this evidence supported the classification ofthis imported case as B.1.1.7. We deposited sequencing data inthe SRA database under accession number PRJNA713811.DISCUSSIONThis case represents one of the first documented introductionsof the B.1.1.7 lineage to South America. More precisely, it wasthe second case after the first registered introduction in Ecuadorby a traveler that returned from the UK on December 13,2020 (7). After that, other South American countries includingArgentina (8), Chile (9), Perú (10), and Brazil (11), have reportedintroductions from the UK. Additionally, local transmission hasbeen already observed in Brazil and Chile (Figure 1B). Thisevidences the rapid transcontinental dissemination of B.1.1.7,that was introduced in South America even before the officialcommunication of the UK government warning about theemergence of this VOC. All these facts highlights that, evenmaximizing border control and complying with the nationaland international protocols for COVID-19 containment, is stillinsufficient to prevent the spread of VOC. The rapid emergenceand spread of VOC need an immediate roll out of surveillancetools to perform an active surveillance. In this sense, the timeperiod between the actual introduction and the official report ofB.1.1.7 cases in South America has a mean of 22.6 days, rangingfrom 1 (Chile) to 51 days (Uruguay) (Figure 1C), evidencing alag in real-time surveillance. This shows the need to improvegenomic surveillance capabilities in the region along with thelogistics to identify cases of particular concern that may requirespecific contingency measures. Thus, there is a need to rapidlydeploy national programs of genomic surveillance at scale settinga goal of sequencing at least 5% of positive samples to detect VOCthat still circulate in low frequency (12).To date, since hospital records and contact tracing numberssignificantly raised in the UK, a salient feature of the B.1.1.7lineage is its increased transmission capacity (13). In this case,the patient did not transmit the virus to their contacts once himarrived in Uruguay. This could be explained by the fact that thesecontacts happened when the patient was asymptomatic (one athis arrival to the airport, and the others after being remittedfrom hospital), being known that asymptomatic patients mightbe less infective than symptomatic patients (14). Another salientfeature of B.1.1.7 is its apparent capacity to cause a more severeillness and to increase the risk of death (2). In this case, thepatient developed symptoms that required hospitalization buthad a positive outcome after receiving moderate care. Together,we conclude that contact tracing and isolation was successful toidentify and quarantine all contacts in adequate time, preventingthe potential spread of this variant in Uruguay. Indeed, ourlab is performing active genomic surveillance of VOC, typinghundreds of COVID-19 positive samples every week and wehave not detected new introductions or local transmissionof B.1.1.7 3 months after the time of this introduction inmid-December, 2020.DATA AVAILABILITY STATEMENTThe datasets presented in this study can be found in onlinerepositories. The names of the repository/repositoriesand accession number(s) can be found in thearticle/supplementary material.ETHICS STATEMENTWritten informed consent was obtained from the individual(s)for the publication of any potentially identifiable images or dataincluded in this article.Frontiers in Virology | www.frontiersin.org 3 May 2021 | Volume 1 | Article 685618Salazar et al. Transcontinental B.1.1.7 Import to UruguayAUTHOR CONTRIBUTIONSCS, AC, IF, PP, DS, and MP-G generated the data and performedthe analyses. AG, BP, VA, and RG collected the data. PM, GM,and GI analyzed the data and wrote the manuscript. All authorscontributed to the article and approved the submitted version.FUNDINGThis work was supported by the Centro de Innovación enVigilancia Epidemiológica (CiVE) from the Institut Pasteurde Montevideo, the Banco de Seguros del Estado (BSE) ofUruguay, and the G4 Research Groups Program from theInstitut Pasteur de Montevideo. Also, this work was supportedby FOCEM (Fondo para la Convergencia Estructural delMercosur) Grant Number: COF 03/11. IF was supported bygrant ANII-POS_NAC_2018_1_151494 from Agencia Nacionalde Investigación e Innovación (ANII), Uruguay.ACKNOWLEDGMENTSWe thank to Nathan D. Grubaugh and Chantal Vogels for theirhelpful collaboration sending their specific primers and probes todetect VOC.REFERENCES1. Public Health England. Investigation of Novel SARS-CoV-2 Variant: Variantof Concern 202012/01 - Technical Briefing 3. (2021). Available onlineat: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/959360/Variant_of_Concern_VOC_202012_01_Technical_Briefing_3.pdf (accessed March 25, 2021).2. Davies NG, Jarvis CI, Edmunds WJ, Jewell NP, Diaz-Ordaz K, KeoghRH. Increased mortality in community-tested cases of SARS-CoV-2 lineage B.1.1.7. Nature. (2021) 539:1–5. doi: 10.1101/2021.02.01.212509593. Grubaugh ND, Hodcroft EB, Fauver JR, Phelan AL, Cevik M. Publichealth actions to control new SARS-CoV-2 variants. Cell. (2021) 184:1127–32. doi: 10.1016/j.cell.2021.01.0444. Quick J. nCoV-2019 Sequencing Protocol v3. (2020). Available online at:https://www.protocols.io/view/ncov-2019-sequencing-protocol-v3-locost-bh42j8ye (accessed April 14, 2021).5. Salazar C, Díaz-Viraqué F, Pereira M, Ferrés I, Moreno P, Moratorio G,et al. Multiple introductions, regional spread and local differentiationduring the first week of COVID-19 epidemic in Montevideo,Uruguay. bioRxiv [Preprint]. (2020). doi: 10.1101/2020.05.09.0862236. Vogels CBF, Breban M, Alpert T, Petrone ME, Watkins AE, HodcroftEB, et al. PCR assay to enhance global surveillance for SARS-CoV-2variants of concern.medRxiv [Preprint]. (2021). doi: 10.1101/2021.01.28.212504867. Ministerio de Salud Pública de Ecuador. Estudios de Secuenciación Genómicadel Inspi Confirman la Presencia de Nueva Variación del SARS-CoV-2 en Ecuador. (2021). Available online at: https://www.salud.gob.ec/estudios-de-secuenciación-genomica-del-inspi-confirman-la-presencia-de-nueva-variación-del-sars-cov-2-en-ecuador (accessed April 14,2021).8. MedicalXPress. Argentina Detects First Case of British Virus Variant. (2021).Available online at: https://medicalxpress.com/news/2021-01-argentina-case-british-virus-variant.html (accessed April 14, 2021).9. Reuters. Chile Records First Case of British Variant of Coronavirus – HealthMinistry. (2020). 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Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 inEngland. Science. (2021) 372:eabg3055. doi: 10.1126/science.abg305514. Sayampanathan AA, Heng CS, Pin PH, Pang J, Leong TY, Lee VJ. Infectivityof asymptomatic versus symptomatic COVID-19. Lancet. (2021) 397:93–4. doi: 10.1016/S0140-6736(20)32651-9Conflict of Interest: The authors declare that the research was conducted in theabsence of any commercial or financial relationships that could be construed as apotential conflict of interest.Copyright © 2021 Salazar, Costabile, Ferrés, Perbolianachis, Pereira-Gómez, Simón,Galiana, Pi, Antelo, García, Moreno, Moratorio and Iraola. This is an open-accessarticle distributed under the terms of the Creative Commons Attribution License (CCBY). The use, distribution or reproduction in other forums is permitted, providedthe original author(s) and the copyright owner(s) are credited and that the originalpublication in this journal is cited, in accordance with accepted academic practice.No use, distribution or reproduction is permitted which does not comply with theseterms.Frontiers in Virology | www.frontiersin.org 4 May 2021 | Volume 1 | Article 685618

Early transcontinental import of SARS-CoV-2 variant of concern 202012/01 (B.1.1.7) from Europe to Uruguay

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Early transcontinental import of SARS-CoV-2 variant of concern 202012/01 (B.1.1.7) from Europe to Uruguay

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