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<article xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" article-type="brief-report"><?properties open_access?><front><journal-meta><journal-id journal-id-type="nlm-ta">Emerg Infect Dis</journal-id><journal-id journal-id-type="iso-abbrev">Emerg Infect Dis</journal-id><journal-id journal-id-type="publisher-id">EID</journal-id><journal-title-group><journal-title>Emerging Infectious Diseases</journal-title></journal-title-group><issn pub-type="ppub">1080-6040</issn><issn pub-type="epub">1080-6059</issn><publisher><publisher-name>Centers for Disease Control and Prevention</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">33567247</article-id><article-id pub-id-type="pmc">8007308</article-id><article-id pub-id-type="publisher-id">21-0138</article-id><article-id pub-id-type="doi">10.3201/eid2704.210138</article-id><article-categories><subj-group subj-group-type="second-type"><subject>Expedited</subject></subj-group><subj-group subj-group-type="heading"><subject>Research Letter</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Letter</subject></subj-group><subj-group subj-group-type="TOC-title"><subject>Novel SARS-CoV-2 Variant in Travelers from Brazil to Japan</subject></subj-group></article-categories><title-group><article-title>Novel SARS-CoV-2 Variant in Travelers from Brazil to Japan</article-title><alt-title alt-title-type="running-head">Novel SARS-CoV-2 Variant in Travelers from Brazil to Japan</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Fujino</surname><given-names>Takahisa</given-names></name></contrib><contrib contrib-type="author"><name><surname>Nomoto</surname><given-names>Hidetoshi</given-names></name></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Kutsuna</surname><given-names>Satoshi</given-names></name></contrib><contrib contrib-type="author"><name><surname>Ujiie</surname><given-names>Mugen</given-names></name></contrib><contrib contrib-type="author"><name><surname>Suzuki</surname><given-names>Tetsuya</given-names></name></contrib><contrib contrib-type="author"><name><surname>Sato</surname><given-names>Rubuna</given-names></name></contrib><contrib contrib-type="author"><name><surname>Fujimoto</surname><given-names>Tsuguto</given-names></name></contrib><contrib contrib-type="author"><name><surname>Kuroda</surname><given-names>Makoto</given-names></name></contrib><contrib contrib-type="author"><name><surname>Wakita</surname><given-names>Takaji</given-names></name></contrib><contrib contrib-type="author"><name><surname>Ohmagari</surname><given-names>Norio</given-names></name></contrib><aff id="aff1">National Center for Global Health and Medicine, Tokyo, Japan (T. Fujino, H. Nomoto, S. Kutsuna, M. Ujiie, T. Suzuki, R. Sato, N. Ohmagari); </aff><aff id="aff2">Tohoku University, Miyagi, Japan (H. Nomoto, T. Suzuki, N. Ohmagari); </aff><aff id="aff3">National Institute of Infectious Diseases, Tokyo (T. Fujimoto, M. Kuroda, T. Wakita)</aff></contrib-group><author-notes><corresp id="cor1">Address for correspondence: Satoshi Kutsuna, Disease Control and Prevention Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan; email: <email xlink:href="sonare.since1192@gmail.com">sonare.since1192@gmail.com</email></corresp></author-notes><pub-date pub-type="ppub"><month>4</month><year>2021</year></pub-date><volume>27</volume><issue>4</issue><fpage>1243</fpage><lpage>1245</lpage><abstract><p>Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with higher transmission potential have been emerging globally, including SARS-CoV-2 variants from the United Kingdom and South Africa. We report 4 travelers from Brazil to Japan in January 2021 infected with a novel SARS-CoV-2 variant with an additional set of mutations.</p></abstract><kwd-group kwd-group-type="author"><title>Keywords: </title><kwd>respiratory infections</kwd><kwd>severe acute respiratory syndrome coronavirus 2</kwd><kwd>SARS-CoV-2</kwd><kwd>SARS</kwd><kwd>COVID-19</kwd><kwd>coronavirus disease</kwd><kwd>zoonoses</kwd><kwd>viruses</kwd><kwd>coronavirus</kwd><kwd>Brazil</kwd><kwd>Japan</kwd></kwd-group></article-meta></front><body><p>Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (<xref rid="R1" ref-type="bibr"><italic>1</italic></xref>), has wreaked havoc worldwide. SARS-CoV-2 causes severe respiratory failure, often rapidly in susceptible patients. Moreover, new variants with estimated higher transmission rates have begun circulating globally, such as Variant of Concern 202012/01 (VOC-202012/01) from the United Kingdom and variant 501Y.V2 from South Africa (<xref rid="R2" ref-type="bibr"><italic>2</italic></xref>). The virulence, reinfection potential, antibody response to, and efficacy of vaccines against these strains, are still unknown, posing a risk for future pandemics. We detected a previously unreported SARS-CoV-2 variant strain in a family arriving in Japan from Brazil.</p><p>On January 2, 2021, a healthy man in his 40s arrived at Haneda Airport, Tokyo, Japan, from Amazonas state in Brazil via Istanbul, Turkey. At the airport quarantine station, he and the 3 family members traveling with him tested positive for SARS-CoV-2 by quantitative real-time reverse transcription PCR. All 4 were asymptomatic and were accommodated in a government-designated quarantine facility to wait out the required 14-day quarantine. </p><p>On day 2 of their visit, a fever of 37.6&#x000b0;C developed in the man; on day 4, the man had a cough. On day 6, his oxygen saturation (SpO<sub>2</sub>) dropped to 93% on ambient air, and he was transferred to the National Center for Global Health and Medicine, a tertiary care hospital in Tokyo, for respiratory failure. The remaining 3 family members remained asymptomatic and continued to stay at the government-designated accommodation. </p><p>At admission, the patient had a cough and mild malaise. Physical examination was almost normal except for late inspiratory crackles in the bilateral lower lung fields. The patient&#x02019;s body temperature was 37.4&#x000b0;C; blood pressure was 113/69 mm Hg and pulse rate 108 beats/min. The patient had a regular respiratory rate of 18 breaths/min and an SpO<sub>2</sub> of 93% on ambient air. Laboratory tests showed a high C-reactive protein level of 10.47 mg/dL (reference range 0.00&#x02013;0.14 mg/dL), but complete blood counts, renal function, liver function, and coagulation tests all were within reference ranges. Chest radiography and computed tomography showed ground-glass opacities in the lower lobes of both lungs. </p><p>We started the patient on treatment with 200 mg remdesivir, a subcutaneous injection of unfractionated heparin, and 6 mg oral dexamethasone on day 1 of admission. On day 2 of admission, the patient&#x02019;s fever subsided, and his general condition improved marginally. On day 3, oxygen therapy was not needed, blood tests showed a decrease in C-reactive protein levels, and no adverse side effects of treatment were observed. He continued treatment with 100 mg/d remdesivir and unfractionated heparin until day 5 of admission and dexamethasone until day 7, during which time we observed no flare-up of symptoms.</p><p>We subjected the SARS-CoV-2 detected in the case-patient and in his family to whole-genome sequencing. Phylogenetic analysis suggested a novel variant (GISAID [<ext-link ext-link-type="uri" xlink:href="https://www.gisaid.org">https://www.gisaid.org</ext-link>] reference no. EPI_ISL_792681) belonging to pangolin lineage P.1 with 12 nonsynonymous mutations including K417T, E484K, and N501Y in the receptor-binding domain of the spike protein (N.R. Faria et al., unpub data, <ext-link ext-link-type="uri" xlink:href="https://virological.org/t/genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-manaus-preliminary-findings/586">https://virological.org/t/genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-manaus-preliminary-findings/586</ext-link>). In addition, the variant strain we detected in the travelers had the N501Y mutation in the receptor-binding site of the spike protein, as noted in VOC-202012/01 and 501Y.V2, and the E484K mutation, similar to that noted in the 501Y strain.</p><p>We did not observe any remarkable difference in the clinical course of this case-patient compared with COVID-19 cases caused by other known SARS-CoV-2 strains. According to multiple modeling analyses, the new VOC-202012/01 variant could be more infectious than previous strains and might have <underline>&#x0003c;</underline>70% increased transmissibility (<xref rid="R3" ref-type="bibr"><italic>3</italic></xref>&#x02013;<xref rid="R5" ref-type="bibr"><italic>5</italic></xref>). Moreover, PCR testing and genomic analysis for this strain suggested an increased viral load in VOC-202012/01 variant. Another strain, 501Y.V2 from South Africa, also has been suggested to have increased transmissibility (H. Tegally et al., unpub. data, <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1101/2020.12.21.20248640">https://doi.org/10.1101/2020.12.21.20248640</ext-link>). However, to date, no definitive evidence has shown that either VOC-202012/01 or 501Y.V2 are associated with more severe COVID-19 cases. </p><p>The symptoms in this patient were relatively mild, although short-term oxygen administration was necessary. Onset of pneumonia a week after the onset of disease also followed the conventional clinical course. However, because the patient was young and had no underlying conditions, this case cannot be generalized.</p><p>In conclusion, we identified a novel variant strain of SARS-CoV-2 in 4 travelers from Brazil. Variant strains are appearing across the world now, and quarantine systems need to be strengthened. We hope to elucidate the infectivity, pathogenicity, and relationship of SARS-CoV-2 variants to vaccines while continuing to take conventional precautions against novel variant strains.</p></body><back><fn-group><fn fn-type="citation"><p><italic>Suggested citation for this article</italic>: Fujino T, Nomoto H, Kutsuna S, Ujiie M, Suzuki T, Sato R, et al. Novel SARS-CoV-2 variant identified in travelers from Brazil to Japan. Emerg Infect Dis. 2021 Apr [<italic>date cited</italic>]. <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3201/eid2704.210138">https://doi.org/10.3201/eid2704.210138</ext-link></p></fn></fn-group><ack><title>Acknowledgments</title><p>We thank Tsuyoshi Sekizuka, Kentaro Itokawa, Masanori Hashino, Nozomu Hanaoka, Nobuo Koizumi, and Tsuguto Fujimoto for assistance with PCR testing and whole-genome sequencing, and we thank the clinical staff at the National Center for Global Health and Medicine for their dedicated clinical practice and patient care.</p><p>This work was supported by the Health, Labor, and Welfare Policy Research Grants, Research on Emerging and Re-emerging Infectious Diseases and Immunization (grant no. 20HA1006).</p></ack><bio id="d39e228"><p>Dr. Fujino is a physician at the National Center for Global Health and Medicine in Shinjuku-ku, Tokyo, Japan. His main research interest is hematology.</p></bio><ref-list><title>References</title><ref id="R1"><label>1. </label><mixed-citation publication-type="webpage"><collab>World Health Organization</collab>. Coronavirus disease (COVID-19) situation reports. Weekly epidemiological update&#x02014;19 January <year>2021</year> [<comment>cited 2021 Jan 21</comment>]. <ext-link ext-link-type="uri" xlink:href="https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports">https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports</ext-link></mixed-citation></ref><ref id="R2"><label>2. </label><mixed-citation publication-type="webpage"><collab>World Health Organization</collab>. SARS-CoV-2 variant [<comment>cited 2021 Jan 21</comment>]. <ext-link ext-link-type="uri" xlink:href="https://www.who.int/csr/don/31-december-2020-sars-cov2-variants/en/">https://www.who.int/csr/don/31-december-2020-sars-cov2-variants/en/</ext-link></mixed-citation></ref><ref id="R3"><label>3. </label><mixed-citation publication-type="webpage"><collab>European Centre for Disease Prevention and Control</collab>. Rapid increase of a SARS-CoV-2 variant with multiple spike protein mutations observed in the United Kingdom; December 20, <year>2020</year> [<comment>cited 2021 Jan 21</comment>]. <ext-link ext-link-type="uri" xlink:href="https://www.ecdc.europa.eu/sites/default/files/documents/SARS-CoV-2-variant-multiple-spikeprotein-mutations-United-Kingdom.pdf">https://www.ecdc.europa.eu/sites/default/files/documents/SARS-CoV-2-variant-multiple-spikeprotein-mutations-United-Kingdom.pdf</ext-link></mixed-citation></ref><ref id="R4"><label>4. </label><mixed-citation publication-type="webpage"><collab>The New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG)</collab>. NERVTAG meeting on SARS-CoV-2 variant under investigation VUI-202012/01. <year>2020</year> Dec 18 [<comment>cited 2021 Jan 21</comment>]. <ext-link ext-link-type="uri" xlink:href="https://app.box.com/s/3lkcbxepqixkg4mv640dpvvg978ixjtf/file/756963730457">https://app.box.com/s/3lkcbxepqixkg4mv640dpvvg978ixjtf/file/756963730457</ext-link></mixed-citation></ref><ref id="R5"><label>5. </label><mixed-citation publication-type="webpage"><collab>New and Emerging Respiratory Virus Threats Advisory Group</collab>. NERVTAG/SPI-M Extraordinary meeting on SARS-CoV-2 variant of concern 202012/01 (variant B.1.1.7). Note of meeting <year>2020</year> Dec 21 [<comment>cited 2021 Jan 21</comment>]. <ext-link ext-link-type="uri" xlink:href="https://app.box.com/s/3lkcbxepqixkg4mv640dpvvg978ixjtf/file/756964987830">https://app.box.com/s/3lkcbxepqixkg4mv640dpvvg978ixjtf/file/756964987830</ext-link></mixed-citation></ref></ref-list></back></article>