VARIANT COMPARISON - Credit Japan's NIID
#15,798
Up until a month ago, we were primarily focused on the UK (B.1.1.7) and South African (B.1.351) variants of concern, although by early January we'd seen a few reports of emerging variants in South America (see Argentina: PAIS Report On COVID E484K Variant In South America and PrePrint: Genomic Evidence of a Sars-Cov-2 Reinfection Case With E484K Spike Mutation in Brazil).
Since then, this new variant - dubbed P.1 - has turned up in more than a dozen countries around the world, including two states inside the U.S. (Minnesota & Oklahoma). 1.On January 10th Japan's National Institute of Infectious Diseases (NIID) announced the discovery of a new COVID Variant among a small group of travelers from Brazil (see Japan: NIID Reporting A New COVID Variant Detected In 4 Travelers From Brazil).
While there are concerns over the transmissibility, and the potential for reinfection from this variant - along with questions over vaccine efficiency - it is too soon to say how much of an impact this P.1. variant may have on the course of the pandemic.
We've 2 early release research letters published in the CDC's EID Journal yesterday, both on imported P.1 variant cases. I've only posted excerpts from each, so follow the links to read them in their entirety.
Volume 27, Number 4—April 2021
Research Letter
Novel SARS-CoV-2 Variant Identified in Travelers from Brazil to Japan
Takahisa Fujino, Hidetoshi Nomoto, Satoshi Kutsuna, Mugen Ujiie, Tetsuya Suzuki, Rubuna Sato, Tsuguto Fujimoto, Makoto Kuroda, Takaji Wakita, and Norio Ohmagari
Abstract
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.
Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (1), 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 (2). 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.
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.
On day 2 of their visit, a fever of 37.6°C developed in the man; on day 4, the man had a cough. On day 6, his oxygen saturation (SpO2) 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.
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’s body temperature was 37.4°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 SpO2 of 93% on ambient air. Laboratory tests showed a high C-reactive protein level of 10.47 mg/dL (reference range 0.00–0.14 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.
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’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.
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 [https://www.gisaid.orgExternal 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, https://virological.org/t/genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-manaus-preliminary-findings/586External 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.
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 <70% increased transmissibility (3–5). Moreover, PCR testing and genomic analysis for this strain suggested an increased viral load in VOC-202012/01 variant.
(SNIP)
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.
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.
Our second stop is a letter describing a family of 3 returning to Italy from São Paulo, Brazil - some 2,000 miles from Amazonas, where the P.1 variant has mostly been detected.
While all three remained asymptomatic, the husband tested positive for SARS-CoV-2 and genomic sequencing of its RBD included the P.1 barcoding mutations K417T, E484K, and N501Y.
Volume 27, Number 4—April 2021
Research Letter
Fabrizio Maggi
Abstract
We report an imported case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant P.1 detected in an asymptomatic traveler who arrived in Italy on an indirect flight from Brazil. This case shows the risk for introduction of SARS-CoV-2 variants from indirect flights and the need for continued SARS-CoV-2 surveillance.
(SNIP)
After visiting São Paulo, Brazil, during November 23, 2020–January 16, 2021, a family, including a 33-year-old man, his 38-year-old wife, and his 7-year-old daughter, flew back to their home in Italy. During their time in Brazil, the family did not travel outside of São Paulo, which is >2,000 miles from Amazonas. The family took an indirect return flight; they flew from São Paulo/Guarulhos International Airport in Brazil to Madrid, Spain, and from there flew to Milan Malpensa Airport in Italy. Molecular tests were performed on all 3 family members at the departure airport in Brazil, and all were SARS negative.
The family arrived in Milan on the afternoon of January 17 and took a train and a car to their home, 30 miles from Milan. Under current recommendations in Italy, all persons entering the country can decide to be screened for SARS-CoV-2. After consulting a general practitioner on January 21, the father went to the hospital for a screening nasopharyngeal swab sample. The sample was tested by using the Alinity platform (Abbott, https://www.abbott.comExternal Link), which returned a positive result for SARS-CoV-2 RNA with a cycle threshold of 23.
(SNIP)
Direct flights from Brazil to Italy were canceled upon the unilateral decision of the government of Italy on January 16, 2021, but our findings confirm the risk for introduction of SARS-CoV-2 variants from indirect flights if no surveillance measures are implemented at arrival. This case also suggests wider circulation of SARS-CoV-2 variant P.1 in areas other than Amazonas in Brazil. P.1-specific primer sets recently have been designed (A. Lopez-Rincon et al., unpub. data, https://doi.org/10.1101/2021.01.20.427043) and will aid in development of large-scale screening programs for this variant.
Prof. Maggi is on the Faculty of Medicine at the University of Insubria and directs the Virology Unit of Ospedale di Circolo and Fondazione Macchi in Varese, Lombardia, Italy. His primary research interest is emerging viral pathogens.
