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      Model-based estimation of transmissibility and reinfection of SARS-CoV-2 P.1 variant

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          Abstract

          Background

          The SARS-CoV-2 variant of concern (VOC) P.1 (Gamma variant) emerged in the Amazonas State, Brazil, in November 2020. The epidemiological consequences of its mutations have not been widely studied, despite detection of P.1 in 36 countries, with local transmission in at least 5 countries. A range of mutations are seen in P.1, ten of them in the spike protein. It shares mutations with VOCs previously detected in the United Kingdom (B.1.1.7, Alpha variant) and South Africa (B.1.351, Beta variant).

          Methods

          We estimated the transmissibility and reinfection of P.1 using a model-based approach, fitting data from the national health surveillance of hospitalized individuals and frequency of the P.1 variant in Manaus from December-2020 to February-2021.

          Results

          Here we estimate that the new variant is about 2.6 times more transmissible (95% Confidence Interval: 2.4–2.8) than previous circulating variant(s). Manaus already had a high prevalence of individuals previously affected by the SARS-CoV-2 virus and our fitted model attributed 28% of Manaus cases in the period to reinfections by P.1, confirming the importance of reinfection by this variant. This value is in line with estimates from blood donors samples in Manaus city.

          Conclusions

          Our estimates rank P.1 as one of the most transmissible among the SARS-CoV-2 VOCs currently identified, and potentially as transmissible as the posteriorly detected VOC B.1.617.2 (Delta variant), posing a serious threat and requiring measures to control its global spread.

          Plain language summary

          SARS-CoV-2, the virus that causes COVID-19, can mutate into variants which might have different characteristics such as increased ability to spread. The P.1 variant, also known as Gamma, was first identified in Manaus, Brazil. Here, we use mathematical and statistical methods to model the spread of P.1 in Manaus and to determine the potential for people getting re-infected with P.1, comparing it to previous circulating variants in the region. We estimate that P.1 spreads 2.6 times more easily than these other variants and that nearly a third of cases over the period studied were reinfections with P.1. These findings help us to understand whether P.1 is likely to be more difficult to control than other variants and what sort of measures might be needed.

          Abstract

          Coutinho et al. use genomic and epidemiological data from Manaus, Brazil, to estimate the transmissibility and potential for reinfection with the SARS-CoV-2 variant-of-concern P.1 (gamma). Using mathematical modelling, the authors estimate that P.1 is 2.6 times more transmissible than previous SARS-CoV-2 variants circulating in Manaus and underlies a large proportion of reinfections in Manaus.

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          Most cited references10

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          Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil

          Despite an extensive network of primary care availability, Brazil has suffered profoundly during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Using daily data from state health offices, Castro et al. analyzed the pattern of spread of COVID-19 cases and deaths in the country from February to October 2020. Clusters of deaths before cases became apparent indicated unmitigated spread. SARS-CoV-2 circulated undetected in Brazil for more than a month as it spread north from S o Paulo. In Manaus, transmission reached unprecedented levels after a momentary respite in mid-2020. Faria et al. tracked the evolution of a new, more aggressive lineage called P.1, which has 17 mutations, including three (K417T, E484K, and N501Y) in the spike protein. After a period of accelerated evolution, this variant emerged in Brazil during November 2020. Coupled with the emergence of P.1, disease spread was accelerated by stark local inequalities and political upheaval, which compromised a prompt federal response. Science , abh1558 and abh2644, this issue p. [Related article:] 821 and p. 815 A variant lineage of SARS-CoV-2 associated with rapid transmission in Manaus, Brazil, evolved in November 2020 with immune escape characteristics. Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.
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            SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis

            Background Viral load kinetics and duration of viral shedding are important determinants for disease transmission. We aimed to characterise viral load dynamics, duration of viral RNA shedding, and viable virus shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in various body fluids, and to compare SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) viral dynamics. Methods In this systematic review and meta-analysis, we searched databases, including MEDLINE, Embase, Europe PubMed Central, medRxiv, and bioRxiv, and the grey literature, for research articles published between Jan 1, 2003, and June 6, 2020. We included case series (with five or more participants), cohort studies, and randomised controlled trials that reported SARS-CoV-2, SARS-CoV, or MERS-CoV infection, and reported viral load kinetics, duration of viral shedding, or viable virus. Two authors independently extracted data from published studies, or contacted authors to request data, and assessed study quality and risk of bias using the Joanna Briggs Institute Critical Appraisal Checklist tools. We calculated the mean duration of viral shedding and 95% CIs for every study included and applied the random-effects model to estimate a pooled effect size. We used a weighted meta-regression with an unrestricted maximum likelihood model to assess the effect of potential moderators on the pooled effect size. This study is registered with PROSPERO, CRD42020181914. Findings 79 studies (5340 individuals) on SARS-CoV-2, eight studies (1858 individuals) on SARS-CoV, and 11 studies (799 individuals) on MERS-CoV were included. Mean duration of SARS-CoV-2 RNA shedding was 17·0 days (95% CI 15·5–18·6; 43 studies, 3229 individuals) in upper respiratory tract, 14·6 days (9·3–20·0; seven studies, 260 individuals) in lower respiratory tract, 17·2 days (14·4–20·1; 13 studies, 586 individuals) in stool, and 16·6 days (3·6–29·7; two studies, 108 individuals) in serum samples. Maximum shedding duration was 83 days in the upper respiratory tract, 59 days in the lower respiratory tract, 126 days in stools, and 60 days in serum. Pooled mean SARS-CoV-2 shedding duration was positively associated with age (slope 0·304 [95% CI 0·115–0·493]; p=0·0016). No study detected live virus beyond day 9 of illness, despite persistently high viral loads, which were inferred from cycle threshold values. SARS-CoV-2 viral load in the upper respiratory tract appeared to peak in the first week of illness, whereas that of SARS-CoV peaked at days 10–14 and that of MERS-CoV peaked at days 7–10. Interpretation Although SARS-CoV-2 RNA shedding in respiratory and stool samples can be prolonged, duration of viable virus is relatively short-lived. SARS-CoV-2 titres in the upper respiratory tract peak in the first week of illness. Early case finding and isolation, and public education on the spectrum of illness and period of infectiousness are key to the effective containment of SARS-CoV-2. Funding None.
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              Estimating the burden of SARS-CoV-2 in France

              France has been heavily affected by the SARS-CoV-2 epidemic and went into lockdown on the 17 March 2020. Using models applied to hospital and death data, we estimate the impact of the lockdown and current population immunity. We find 3.6% of infected individuals are hospitalized and 0.7% die, ranging from 0.001% in those 80ya. Across all ages, men are more likely to be hospitalized, enter intensive care, and die than women. The lockdown reduced the reproductive number from 2.90 to 0.67 (77% reduction). By 11 May 2020, when interventions are scheduled to be eased, we project 2.8 million (range: 1.8–4.7) people, or 4.4% (range: 2.8–7.2) of the population, will have been infected. Population immunity appears insufficient to avoid a second wave if all control measures are released at the end of the lockdown.
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                Author and article information

                Contributors
                renato.coutinho@ufabc.edu.br
                flamarquitti@gmail.com
                Journal
                Commun Med (Lond)
                Commun Med (Lond)
                Communications Medicine
                Nature Publishing Group UK (London )
                2730-664X
                15 November 2021
                15 November 2021
                2021
                : 1
                : 48
                Affiliations
                [1 ]GRID grid.412368.a, ISNI 0000 0004 0643 8839, Universidade Federal do ABC, ; Santo André, Brazil
                [2 ]Observatório COVID-19 BR, São Paulo, Brazil
                [3 ]GRID grid.411087.b, ISNI 0000 0001 0723 2494, Universidade Estadual de Campinas, ; Campinas, Brazil
                [4 ]GRID grid.410543.7, ISNI 0000 0001 2188 478X, Universidade Estadual Paulista, ; São Paulo, Brazil
                [5 ]Vigilância Epidemiológica, Secretaria de Saúde de Florianópolis, Florianópolis, Brazil
                [6 ]GRID grid.11899.38, ISNI 0000 0004 1937 0722, Universidade de São Paulo, ; São Paulo, Brazil
                [7 ]GRID grid.416738.f, ISNI 0000 0001 2163 0069, Centers for Disease Control and Prevention, ; Atlanta, GA USA
                [8 ]GRID grid.411204.2, ISNI 0000 0001 2165 7632, Universidade Federal do Maranhão, ; São Luís, Brazil
                [9 ]GRID grid.419014.9, ISNI 0000 0004 0576 9812, Faculdade de Ciências Médicas da Santa Casa de São Paulo, ; São Paulo, Brazil
                Author information
                http://orcid.org/0000-0003-0510-3992
                http://orcid.org/0000-0002-9023-0031
                http://orcid.org/0000-0001-7707-8859
                Article
                48
                10.1038/s43856-021-00048-6
                9053218
                572d68fb-893d-4e12-9dbd-c696ec6f0b3b
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 16 April 2021
                : 27 October 2021
                Funding
                Funded by: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
                Categories
                Article
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                © The Author(s) 2021

                viral infection,dynamical systems
                viral infection, dynamical systems

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