key: cord-0906235-p40s0h6q authors: Nonaka, Carolina Kymie Vasques; Gräf, Tiago; Barcia, Camila Araújo de Lorenzo; Costa, Vanessa Ferreira; de Oliveira, Janderson Lopes; Passos, Rogério da Hora; Bastos, Iasmin Nogueira; de Santana, Maria Clara Brito; Santos, Ian Marinho; de Sousa, Karoline Almeida Felix; Weber, Thamires Gomes Lopes; de Siqueira, Isadora Cristina; Rocha, Clarissa Araújo Gurgel; Mendes, Ana Verena Almeida; Souza, Bruno Solano de Freitas title: SARS-CoV-2 variant of concern P.1 (Gamma) infection in young and middle-aged patients admitted to the intensive care units of a single hospital in Salvador, northeast Brazil, February 2021 date: 2021-08-11 journal: Int J Infect Dis DOI: 10.1016/j.ijid.2021.08.003 sha: f70bfca770b637c4df5d54a73ca70f3b35c3f515 doc_id: 906235 cord_uid: p40s0h6q OBJECTIVES: To evaluate changes in COVID-19 patients' characteristics occurring after the emergence of the SARS-CoV-2 variant of concern (VOC) P.1 (Gamma) by comparing the clinical, demographic and laboratory profile of patients hospitalized during the first (May-July 2020) and second (December 2020 - February 2021) pandemic waves. METHODS: Data was collected from records of COVID-19 patients (n=4164) admitted to a single hospital in Salvador, Northeast Brazil. SARS-CoV-2 genome sequencing was performed in nasopharyngeal swab samples from 12 patients with age < 60 years-old admitted to the intensive care units (ICU) in February 2021. RESULTS: From June 2020 to February 2021, the median age of patients admitted in the ICU decreased from 66 to 58 years (p<0.05), accompanied by an increased proportion of patients without comorbidities (15.32% vs 32.20%, p<0.0001). A significant reduction in the Ct values of SARS-CoV-2 RT-PCR tests was observed in the second wave (p<0.0001). Sequencing analysis detected lineage Gamma in all 12 ICU patients sampled in February 2021. CONCLUSION: Our results demonstrated an increased proportion of younger adults without comorbidities with severe disease during the second COVID-19 wave, shortly after the confirmation of local Gamma circulation. New SARS-CoV-2 variants have shown concern regarding their increased infectivity and possible immune escape 1 in Amazonas state, Gamma was responsible for a public health calamity in this state 5, 6 . Currently, Gamma is being detected at increasing rates from January 2021 on throughout Brazil, becoming the predominant lineage associated with the second wave of infections (http://www.genomahcov.fiocruz.br). Following an acceleration of the transmission rates in 2021, Brazil has become the epicenter of the COVID-19 pandemic, with over 13 million confirmed cases and 350,000 deaths (https://www.covid.saude.gov.br). Gamma has 21 lineage-defining mutations, including ten in the spike protein, three of them in the RBD (K417T, E484K and N501Y), showing a surprising convergence with the B.1.351 RBD. These three mutations in the RBD combined were shown to increase the receptor binding affinity 7 . The mutations found in Gamma were associated with increased transmissibility 6 , higher viral load 5 and propensity for immune evasion 8 and SARS-CoV-2 reinfection 9 . Along with the dissemination of Gamma, there were also reports of an increased percentage of young patients evolving with severe disease 8 . However, many other questions remain unanswered, including possible increased fatality rate, disease severity in people without known SARS-CoV-2 risk comorbidities, reduced time of evolution from the first symptoms, and hospitalization. Recently, public health authorities in the state of Bahia (Northeast Brazil) have confirmed the circulation of Gamma in the state. The first reports of Gamma detection in Salvador date from late December 2020 and early January 2021, and they are linked to individuals with travel history to Manaus 10 . This was followed by a rampant increase in the number of hospitalizations and deaths due to COVID-19 in Bahia in February and March 2021 (https://bi.saude.ba.gov.br/transparencia/). However, the clinical and demographic features of this epidemic second wave, as well as the association with SARS-CoV-2 lineages are still up to be characterized. Herein, we report changes in the profile of patients admitted in the intensive care unit, due to COVID-19, in a private hospital in Salvador, Bahia capital city, in February 2021, with possible involvement of the local circulation of the Gamma variant of concern. A cross-sectional study was performed at the São Rafael Hospital, a reference private general hospital in Salvador, Bahia, Northeast Brazil. Two time periods with increased numbers of hospital admissions were selected for data analysis, corresponding to the first wave (May-July Gamma detected genomes and tree branch support was calculated with the Shimodaira-Hasegawa approximate likelihood ratio test (SH-aLRT), as previously described 11 . Background high quality (>29,000bp and <1% N) Brazilian Gamma sequences were obtained in the EpiCoV database in GISAID as available on March 25, 2021 (Supplementary Table S1 ) and aligned with the genomes generated here in MAFFT 12 . The ML tree was visualized using the FigTree v1.4 (http://tree.bio.ed.ac.uk/software/figtree/). Categorical variables were compared using the Fisher test. Continuous data were presented as median and 95% CI; Mann-Whitney and Kruskal-Wallistest tests were used for comparisons between nonparametric data (Ct values and median age). P values<0.05 were considered significant. Data were analyzed with Prism software (v.9.1, GraphPad). Accompanying the evolution of the pandemic in the city of Salvador, data analysis demonstrated two waves of admission due to COVID-19 at the hospital, the first comprising (Figure 2A) . A progressive increase in the percentage of patients with age lower than 60 years-old being admitted to the ICU was observed in the second wave, differing from the demographic pattern observed in the first wave ( Figure 2B ). Along with the increase in the percentage of young and middle-aged patients, there was also an increased percentage of patients entering the ICU without known comorbidities (cardiovascular diseases, hypertension, diabetes, obesity, hepatic diseases, asthma, kidney diseases and immunosuppression). Patients without comorbidities represented 32.20% of hospitalized COVID-19 patients admitted to the ICU due to COVID-19 in February 2021, compared to 15.32% in June 2020 (p<0.0001). Table 1 shows the frequency of patients with different comorbidities stratified by age group. Recently, researchers reported a significant increase in case fatality rates among young and middle-age adults in Parana, Brazil which may be associated with the Gamma strain 16 . The data presented herein also gives support to a role of variant Gamma in the acceleration of the pandemic in Salvador and Bahia state seen in early 2021. It is notable the observed increase in the percentage of patients being admitted in the ICU with no risk factors for severe COVID-19, such as increased age, hypertension, diabetes, among others 16 . This data, however, is preliminary and more studies are necessary and urgent to clarify if changes in the virulence may be attributable to Gamma. Also, it is necessary to investigate the influence of vaccine roll out, which started in mid-January, first recruiting healthcare workers and progressing to elderly individuals with age superior to 80 years-old by the end of February, utilizing either Coronavac, a two dose, 28-day interval vaccine scheme or Astrazeneca's ChAdOx nCoV-19, a two dose, 3-month interval vaccine scheme. Therefore, during the period evaluated in this study, a very low percentage of elderly patients had received two doses of the vaccine. Although Ct values are subjected to intrinsic sample collection variability and do not utilize reference measurements, the comparison of the results found in the peaks of the first wave and the second wave suggest that patients presented increased viral load in February 2021, which was also reported when Gamma samples were compared to non-Gamma samples 17, 7 . Confirming that Gamma is a highly transmissible variant, associated with increased viral replication and disease severity would require restrictive control measures to be revisited in populations with confirmed Gamma circulation, to adequately prevent viral spread and pressure to the healthcare system, as has been observed in Brazil. The data presented herein does not give support to an increase mortality rate among hospitalized COVID-19 patients after the emergency of Gamma, since mortality rates and IMV rates decreased in the evaluated period. Since this data may be influenced by other confounders, such as improved disease management and evolving therapeutic protocols, future studies properly designed to answer whether Gamma may be associated with any changes in disease severity. In summary, our findings contribute to describe the characteristics of the patients with severe COVID-19 during the second wave, which appears to be associated with an increased proportion of young and middle-aged adults. Additionally, suggests that the Gamma variant may have rapidly spread in Salvador, Brazil, leading to increased number of cases, hospitalization and ICU admissions shortly after its first detection in Bahia state. These preliminary findings reinforce the immediate need to adopt measures to reduce its spread and more rapid vaccination. The authors claim no conflict of interest. This study was funded by CNPq, Inova Fiocruz, Serrapilheira Institute and the D'Or Institute for Research and Education. This study was reviewed by local IRBs and received ethical approval by the National Committee for Ethics on Research (CONEP; CAAE: 29496920.8.0000.5262, 46821621.5.0000.0048 and 3.980.128 /2020). All sampled patients have provided written informed consent. Writing Rapid identification and tracking of SARS-CoV-2 variants of concern. The Lancet SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus Evolutionary Dynamics and Dissemination Pattern of the SARS-CoV-2 Lineage B.1.1.33 During the Early Pandemic Phase in Brazil Evolution and epidemic spread of SARS-CoV-2 in Brazil Genomics and epidemiology of a novel SARS-CoV-2 lineage in Manaus, Brazil Phylogenetic relationship of SARS-CoV-2 sequences from Amazonas with emerging Brazilian variants harboring mutations E484K and N501Y in the Spike protein Molecular dynamic simulation reveals E484K mutation enhances spike RBD-ACE2 affinity and the 1 combination of E484K, K417N and N501Y mutations (501Y.V2 variant) induces conformational 2 change greater than N501Y mutant alone Antibody evasion by the Brazilian P.1 strain of SARS-CoV-2. bioRxiv preprint Three SARS-CoV-2 reinfection cases by the new Variant of Concern (VOC) P.1/501Y.V3. Res Sq Early genomic detection of SARS-CoV-2 P. 1 variant in Northeast Brazil IQ-TREE 2: New Models and Efficient Methods for Phylogenetic Inference in the Genomic Era MAFFT multiple sequence alignment software version 7: improvements in performance and usa-bility Genomic monitoring unveil the early detection of the SARS-CoV-2 B.1.351 lineage (20H/501Y.V2) in Brazil COVID-19 herd immunity in the Brazilian Amazon Resurgence of COVID-19 in Manaus, Brazil, despite high seroprevalence Sudden rise in COVID-19 case fatality among young and middle-aged adults in the south of Brazil after identification of the novel B 1 (P. 1) SARS-CoV-2 strain: analysis of data from the state of Parana. medRxiv Genomics and epidemiology of a novel SARS-CoV-2 lineage in Manaus SARS-CoV-2 variant of concern P.1 infection in young and middle-aged We thank Ms. Roquelina Assis for technical support, the team of the Molecular Biology laboratory of São Rafael Hospital for sample handling, and Jessica Pronestino for assistance in statistical analysis. The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest, or non-financial interest in the subject matter or materials discussed in this manuscript.