key: cord-1020117-eym1u7h5
authors: Barbosa, G.; Moreira, L. V. L.; Justo, A. F. O.; Perosa, A. H.; Chaves, A. P.; Bueno, M. S.; de Souza Luna, L. K.; Conte, D. D.; Carvalho, J. M.; Prates, J.; Dantas, P. S.; Faico, K.; Camargo, C.; Resende, P. C.; Siqueira, M.; Bellei, N. c. j.
title: Rapid spread and high impact of the Variant of Concern P.1 in the largest city of Brazil
date: 2021-04-14
journal: nan
DOI: 10.1101/2021.04.10.21255111
sha: 78bf0b28561a5464569c95eabcac860638a2bdde
doc_id: 1020117
cord_uid: eym1u7h5

First in Manaus in the Brazilian Northern region, the Variant of Concern P.1 traveled 3800 kilometers southeast to endanger Sao Paulo contributing to the collapse of the health system. Here, we show evidence of how fast the VOC P.1 has spread in the most populated city in South America.

. CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 14, 2021. . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The COVID-19 has reached over 131 million cases around the world, with more than 2.8 million of death, according to the World Health Organization (1). As the SARS-CoV-2 cases continue to emerge globally, variants of concern (VOC) and variants of interest (VOI) have been described (2). The variants share important points of mutations at the receptor-binding domain (RBD) of the Spike protein, which might increase the transmissibility of COVID-19 and promote escape from neutralizing

Brazil is currently the epicenter of COVID-19, with more than 13 million confirmed cases of April 2021(1). Two variants, VOC P.1 and VOI P.2, evolved from lineage B.1.1.28, have taken over the scene since late 2020 in the country (4,5). The VOC P.1 was first detected in January 2021 in Japanese travelers returning from Manaus and was responsible for the second wave in Amazonas in late November 2020 (5) . In October 2020, the VOI P.2 was reported in Rio de Janeiro and was estimated to have emerged in late August 2020 (5,6). Both variants have been associated also with reinfection cases (6).

Paulo city, during the first week of March, 64.4% of samples were identified as P.1. The investigation of lineages not only contributes to epidemiological surveillance but also provides a better comprehension of the spread and circulation of variants, allowing the association to clinical outcomes and response to vaccines (7) . In this sense, we aimed to investigate the spread of P.1 and P.2 variants in samples from hospitalized patients (HP) and healthcare workers (HCW) attended in a university hospital in São Paulo city.

This study was conducted in compliance with institutional guidelines, approved by the Of the 60 selected samples, 52 whole genome sequences were generated (30 from HP and 22 from HCW) following the sequencing protocol using the Illumina MiSeq platform and the analysis pipeline described by Resende et al (8) . The SARS-CoV-2 lineages were classified by the PANGO lineages nomenclature (9) . Genome . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 14, 2021. There is a broad discussion about whether the available vaccines against SARS-CoV-2 will be less effective at preventing infection with the emerging variants (10) . In this work, 14 samples (26.9%) of the 52 sequenced samples were from individuals that had received at least one dose of vaccine, ChAdOx1-S/nCoV-19 (n=2) or SINOVAC (n=26). Although they were vaccinated, they could not be considered immunized, regarding the days after vaccination.

Among the hospitalized patients, 19 (63%) were admitted to the intensive care unit, from which nine were discharged and ten died. Comparing the RT-PCR Ct values of all attended patients since the first wave, we did not observe any difference in the Ct mean values with those of P.1 (data not shown). May 2020 registered the peak of number of positive cases with a Ct mean of 23.6. Now, as of April 2021, we are facing a rise in the number of cases. However, the Ct mean was 24.9, which may indicate that the spread of P.1 does not contribute to an actual increase in the viral load.

There is still a need for more epidemiologic surveys to assure the role of the VOCs in transmission and escape to neutralizing antibodies. Our findings emphasize that the P.1 variant has spread widely throughout the country. Despite all actions of interventions such as the use of masks, physical distancing, flight travel reductions, and the currently established lockdown in São Paulo, the frequency rates of P.1 increased significantly in two weeks, evidencing its fast spread.

. CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted April 14, 2021. ; https://doi.org/10.1101/2021.04.10.21255111 doi: medRxiv preprint

SARS-CoV-2 Variants of Concern

The ongoing evolution of variants of concern and interest of SARS-CoV-2 in Brazil revealed by convergent indels in the amino (N)-terminal domain of the Spike protein -SARS-CoV-2 coronavirus / nCoV-2019 Genomic Epidemiology -Virological. VirologicalOrg [Internet]. 2021;1-37

Genomic characterization of a novel SARS-CoV-2 lineage from Rio de Janeiro, Brazil

COVID-19 epidemic in the Brazilian state of Sq

Spike E484K mutation in the first SARS-CoV-2 reinfection case confirmed in Brazil

Genomic Epidemiology -Virological

SARS-CoV-2 Variants of Concern in the United States-Challenges and Opportunities

SARS-CoV-2 genomes recovered by long amplicon tiling multiplex approach using nanopore sequencing and applicable to other sequencing platforms

A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology

Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7

The authors wish to thank all the health care workers and scientists who have worked hard to deal with this pandemic threat, in special the sequencing team from Laboratory of Respiratory Viruses and Measles, Oswaldo Cruz Institute and the Fiocruz COVID-19Genomic Surveillance Network (http://www.genomahcov.fiocruz.br/). This work was supported by grant 2020/11719-0, São Paulo Research Foundation (FAPESP) and Coordination for the Improvement of Higher Education Personnel CAPES.

No potential conflict of interest was reported by the author(s).

Amazonas was driven by long-term persistence of endemic SARS-CoV-2 lineages and the recent emergence of the new Variant of Concern P . 1. Res Sq . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)The copyright holder for this preprint this version posted April 14, 2021. ; https://doi.org/10.1101/2021.04.10.21255111 doi: medRxiv preprint It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 14, 2021. ; https://doi.org/10.1101/2021.04.10.21255111 doi: medRxiv preprint . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 14, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 14, 2021. ; https://doi.org/10.1101/2021.04.10.21255111 doi: medRxiv preprint