key: cord-0915562-q6mspi5a
authors: Campoy, Pedro J. Sola; Buenestado-Serrano, Sergio; Pérez-Lago, Laura; Rodriguez-Grande, Cristina; Catalán, Pilar; Andrés-Zayas, Cristina; Alcalá, Luis; Losada, Carmen; Rico-Luna, Carla; Muñoz, Patricia; de Viedma, Darío García
title: Primeras importaciones de las variantes SARS-CoV-2 P.1 y P.2 de Brasil a Madrid y transmisión comunitaria
date: 2021-06-03
journal: Enferm Infecc Microbiol Clin
DOI: 10.1016/j.eimc.2021.05.008
sha: 5a188bbe284fc143ccf5591d2731a4a32d383769
doc_id: 915562
cord_uid: q6mspi5a

Introduction: SARS-CoV-2 variants of concern (VOC) have been described in the UK (B.1.1.7), South Africa (B.1.351) and Brazil (P.1). Among them, the most scarce information has been obtained from the P.1 variant and more data on its global presence and about its spreading dynamics are needed. Methods: Whole genome sequencing was performed prospectively on travellers arriving from Brasil and on a random selection of SARS-CoV-2 positive cases from our population. Results: In this study we report the first SARS-CoV-2 P.1 and P.2 variants exported from Brazil to Spain. The case infected with the P.1 variant, who had only stayed in Rio de Janeiro, required hospitalization. The two P.2 cases remained asymptomatic. A wider distribution for P.1 variant beyond the Brazilian Amazonia should be considered. The exportation of the P.2 variant, carrying the E484K mutation, deserves attention. Conclusion: One month after the first description of P.1 and P.2 importations from Brazil to Madrid, these variants were identified circulating in the community, in cases without a travel history, and involved in household transmissions.

J o u r n a l P r e -p r o o f 3 Summary Introduction: SARS-CoV-2 variants of concern (VOC) have been described in the UK (B.1.1.7), South Africa (B.1.351) and Brazil (P.1). Among them, the most scarce information has been obtained from the P.1 variant and more data on its global presence and about its spreading dynamics are needed.

Methods: Whole genome sequencing was performed prospectively on travellers arriving from Brasil and on a random selection of SARS-CoV-2 positive cases from our population.

Results: In this study we report the first SARS-CoV-2 P.1 and P.2 variants exported from Brazil to Spain. The case infected with the P.1 variant, who had only stayed in Rio de Janeiro, required hospitalization. The two P.2 cases remained asymptomatic. A wider distribution for P.1 variant beyond the Brazilian Amazonia should be considered. The exportation of the P.2 variant, carrying the E484K mutation, deserves attention.

Conclusion: One month after the first description of P.1 and P.2 importations from Brazil to Madrid, these variants were identified circulating in the community, in cases without a travel history, and involved in household transmissions.

Keywords: COVID-19, SARS-CoV-2, P1, P2, importation, travellers.

Resumen Introducción: Se han descrito "variantes de preocupación" (COV) de SARS-CoV-2 en el Reino Unido (B.1.1.7), Sudáfrica (B.1.351) y Brasil (P.1). Entre ellas, se dispone de información más escasa para la variante P.1 y se necesitan más datos sobre su presencia global y sobre su dinámica de expansión.

Métodos: Se realizó secuenciación del genoma completo de forma prospectiva de SARS-COV-2 en viajeros procedentes de Brasil y en una selección aleatoria de casos positivos de SARS-CoV-2 de nuestra población.

Resultados: En este estudio reportamos las primeras variantes de SARS-CoV-2 P.1 y P.2 exportadas desde Brasil a España. El caso infectado por la variante P.1, que solo había permanecido en Río de Janeiro, requirió hospitalización. Los dos casos P.2 permanecieron asintomáticos. Se debe considerar una distribución más amplia para la variante P.1 más allá de la Amazonía brasileña. La exportación de la variante P.2, que porta la mutación E484K, merece asimismo atención adicional.

Conclusión: Un mes después de la primera descripción de las importaciones de P.1 y P.2 de Brasil a Madrid, se identificaron estas variantes circulando en la comunidad, en casos sin antecedentes de viaje, e implicadas en transmisiones domiciliarias.

Palabras clave: COVID-19, SARS-CoV-2, P1, P2, importación, viajeros. SARS-CoV-2 variants of concern (VOC) have been described in the UK (B.1.1.7), South Africa (B.1.351), and Brazil (P.1) (1). They harbour a constellation of mutations with potential significance, some mapping in the receptor binding domain of the spike protein, possibly involved in immune evasion or increase of the affinity for ACE2 receptor (2, 3) .

The fact that different SARS-CoV-2 lineages share relevant mutations suggests a convergent evolution towards an advantageous phenotype. A more efficient transmission rate and an increased mortality (4) have been found for B.1.1.7, the most extensively studied VOC, currently being the major lineage in the UK (5), and present in 83 countries (1).

Not so much information is available for the P.1 variant (6). Sequencing efforts for P.1 have been less intensive in Brazil than for B.1.1.7 variant in the UK. In the moment of writing this article it had only been detected in 940 cases from 26 countries, with barely two exportation events reported, to Japan and Italy (7, 8) . Therefore, more data on the global presence of the P.1 variant and about its spreading dynamics are needed.

We present the analysis of three travellers who flew from Brazil to Madrid separately on January 29 and 31, 2021. All were asymptomatic upon arrival and were diagnosed at the airport (antigenic test) within a screening program. They were transferred to our hospital and positive RT-PCR (TaqPath COVID-19, ThermoFisher) confirmed the initial diagnosis.

Due to the alarm of the potential import of the P.1 VOC from Brazil, urgent sequencing was activated. Whole genome sequencing was performed with the Artic_nCov-2019_V3 panel of primers. Libraries were prepared using the Nextera Flex DNA Library Preparation Kit (Illumina lnc, California, USA) and sequenced in a the variants involved. It allowed us to determine that one of the travellers (Case 1) carried the P.1 variant (Figure 1a) , after confirming that it harboured all 17 P.1 marker-SNPs.

Case 1 was a 44-year-old male who had stayed in Rio de Janeiro for 15 days living with another relative who did not develop COVID-19. He had no contact with COVID-19 cases nor other social interactions. He developed symptoms (fever, cough, pain in the left hemithorax) two days after his positive RT-PCR and had to be hospitalized the day after the symptoms began, due to a bilateral pneumonia, requiring supplemental oxygen. He was treated with methylprednisolone and baricitinib (hepatitis ruled out anakinra/tocilizumab), with clinical improvement. For the P.1 case reported in Japan (7), only the father (in his 40s) of the travelling family developed relatively mild symptoms, while the remaining three relatives remained asymptomatic.

The other published case (33 years of age), who exported P.1 to Italy, remained asymptomatic (8).

The P-1 case reported in this study had only stayed in Rio and the case reported in Italy had not left Sao Paolo. These data indicate that the P.1 variant is probably more widely distributed in Brazil and not only restricted to the Amazonia as initially considered (9) . The P.1 variant was also identified from his daughter´s specimen (0 SNPs between the P.1 variants from Cases 5 and 6, indicating household transmisssion), whereas the high Ct values for his partner´s specimen did not allow performing WGS. In the telephonic epidemiological survey, they did not refer any history of travelling or contacts with other travellers or foreigners, indicating the community nature of these P.1 variants.

We report three independent COVID-19 imported cases from Brazil to Spain.

To the best of our knowledge, one represents the first imported P.1 SARS-CoV-2 variant to Spain and was associated to a severe disease. The patient had only stayed in Rio de Janeiro, for which reason a wider distribution for the P.1 variant, beyond the Amazonia, should be considered in Brazil. The P.2 variant carrying the E484K concern mutation is also reported here, imported by two other travellers who remained asymptomatic. One month after the first description of P.1 and P.2 importations from Brazil to Madrid, these variants were identified circulating in the community, in cases without a travel history, and involved in household transmissions. Our findings add information to the scarce data available to date on SARS-CoV.2 concern variants emerging in Brazil. 

Marañón Microbiology-ID COVID-19 Study Group

Aldámiz (Teresa), Alonso (Roberto)

Burillo (Almudena), Candela (Ana), Carrillo (Raquel)

Cobos (Alejandro), Díez (Cristina), Escribano (Pilar), Estévez (Agustín)

Guillén (Helmuth) Guinea (Jesús)

Machado (Marina), Marín (Mercedes), Martín (Pablo)

Pescador (Paula)

Sánchez (Carlos), Sánchez (Mar)

Vesperinas (Lara)

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This work was supported by Instituto de Salud Carlos III (Ref COV20/00140:

and by Consejo Superior de Investigaciones Científicas (CSIC) (PTI Salud Global). We are grateful to Dainora Jaloveckas (cienciatraducida.com) for editing and proofreading assistance. We are indebted to Rocío Fernandez del Rey and Maricela Valerio for her valuable help to acquire epidemiological and clinical data.