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      Mouthwashes with CPC Reduce the Infectivity of SARS-CoV-2 Variants In Vitro

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          Abstract

          Oral mouthwashes decrease the infectivity of several respiratory viruses including SARS-CoV-2. However, the precise agents with antiviral activity in these oral rinses and their exact mechanism of action remain unknown. Here we show that cetylpyridinium chloride (CPC), a quaternary ammonium compound in many oral mouthwashes, reduces SARS-CoV-2 infectivity by inhibiting the viral fusion step with target cells after disrupting the integrity of the viral envelope. We also found that CPC-containing mouth rinses decreased more than a thousand times the infectivity of SARS-CoV-2 in vitro, while the corresponding vehicles had no effect. This activity was effective for different SARS-CoV-2 variants, including the B.1.1.7 or Alpha variant originally identified in United Kingdom, and in the presence of sterilized saliva. CPC-containing mouth rinses could therefore represent a cost-effective measure to reduce SARS-CoV-2 infectivity in saliva, aiding to reduce viral transmission from infected individuals regardless of the variants they are infected with.

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          Virological assessment of hospitalized patients with COVID-2019

          Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 20191,2. Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses3. This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung2,4; the same receptor tropism is thought to have determined the pathogenicity-but also aided in the control-of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission6-8. There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 108 RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples-in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19.
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            Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England

            Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the capacity to generate variants with major genomic changes. The UK variant B.1.1.7 (also known as VOC 202012/01) has many mutations that alter virus attachment and entry into human cells. Using a variety of statistical and dynamic modeling approaches, Davies et al. characterized the spread of the B.1.1.7 variant in the United Kingdom. The authors found that the variant is 43 to 90% more transmissible than the predecessor lineage but saw no clear evidence for a change in disease severity, although enhanced transmission will lead to higher incidence and more hospital admissions. Large resurgences of the virus are likely to occur after the easing of control measures, and it may be necessary to greatly accelerate vaccine roll-out to control the epidemic. Science , this issue p. eabg3055 The major coronavirus variant that emerged at the end of 2020 in the UK is more transmissible than its predecessors and could spark resurgences. INTRODUCTION Several novel variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, emerged in late 2020. One of these, Variant of Concern (VOC) 202012/01 (lineage B.1.1.7), was first detected in southeast England in September 2020 and spread to become the dominant lineage in the United Kingdom in just a few months. B.1.1.7 has since spread to at least 114 countries worldwide. RATIONALE The rapid spread of VOC 202012/01 suggests that it transmits more efficiently from person to person than preexisting variants of SARS-CoV-2. This could lead to global surges in COVID-19 hospitalizations and deaths, so there is an urgent need to estimate how much more quickly VOC 202012/01 spreads, whether it is associated with greater or lesser severity of disease, and what control measures might be effective in mitigating its impact. We used social contact and mobility data, as well as demographic indicators linked to SARS-CoV-2 community testing data in England, to assess whether the spread of the new variant may be an artifact of higher baseline transmission rates in certain geographical areas or among specific demographic subpopulations. We then used a series of complementary statistical analyses and mathematical models to estimate the transmissibility of VOC 202012/01 across multiple datasets from the UK, Denmark, Switzerland, and the United States. Finally, we extended a mathematical model that has been extensively used to forecast COVID-19 dynamics in the UK to consider two competing SARS-CoV-2 lineages: VOC 202012/01 and preexisting variants. By fitting this model to a variety of data sources on infections, hospitalizations, and deaths across seven regions of England, we assessed different hypotheses for why the new variant appears to be spreading more quickly, estimated the severity of disease associated with the new variant, and evaluated control measures including vaccination and nonpharmaceutical interventions. Combining multiple lines of evidence allowed us to draw robust inferences. RESULTS The rapid spread of VOC 202012/01 is not an artifact of geographical differences in contact behavior and does not substantially differ by age, sex, or socioeconomic stratum. We estimate that the new variant has a 43 to 90% higher reproduction number (range of 95% credible intervals, 38 to 130%) than preexisting variants. Similar increases are observed in Denmark, Switzerland, and the United States. The most parsimonious explanation for this increase in the reproduction number is that people infected with VOC 202012/01 are more infectious than people infected with a preexisting variant, although there is also reasonable support for a longer infectious period and multiple mechanisms may be operating. Our estimates of severity are uncertain and are consistent with anything from a moderate decrease to a moderate increase in severity (e.g., 32% lower to 20% higher odds of death given infection). Nonetheless, our mathematical model, fitted to data up to 24 December 2020, predicted a large surge in COVID-19 cases and deaths in 2021, which has been borne out so far by the observed burden in England up to the end of March 2021. In the absence of stringent nonpharmaceutical interventions and an accelerated vaccine rollout, COVID-19 deaths in the first 6 months of 2021 were projected to exceed those in 2020 in England. CONCLUSION More than 98% of positive SARS-CoV-2 infections in England are now due to VOC 202012/01, and the spread of this new variant has led to a surge in COVID-19 cases and deaths. Other countries should prepare for potentially similar outcomes. Impact of SARS-CoV-2 Variant of Concern 202012/01. ( A ) Spread of VOC 202012/01 (lineage B.1.1.7) in England. ( B ) The estimated relative transmissibility of VOC 202012/01 (mean and 95% confidence interval) is similar across the United Kingdom as a whole, England, Denmark, Switzerland, and the United States. ( C ) Projected COVID-19 deaths (median and 95% confidence interval) in England, 15 December 2020 to 30 June 2021. Vaccine rollout and control measures help to mitigate the burden of VOC 202012/01. A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, VOC 202012/01 (lineage B.1.1.7), emerged in southeast England in September 2020 and is rapidly spreading toward fixation. Using a variety of statistical and dynamic modeling approaches, we estimate that this variant has a 43 to 90% (range of 95% credible intervals, 38 to 130%) higher reproduction number than preexisting variants. A fitted two-strain dynamic transmission model shows that VOC 202012/01 will lead to large resurgences of COVID-19 cases. Without stringent control measures, including limited closure of educational institutions and a greatly accelerated vaccine rollout, COVID-19 hospitalizations and deaths across England in the first 6 months of 2021 were projected to exceed those in 2020. VOC 202012/01 has spread globally and exhibits a similar transmission increase (59 to 74%) in Denmark, Switzerland, and the United States.
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              Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7

              The COVID-19 pandemic has had widespread effects across the globe, and its causative agent, SARS-CoV-2, continues to spread. Effective interventions need to be developed to end this pandemic. Single and combination therapies with monoclonal antibodies have received emergency use authorization1-3, and more treatments are under development4-7. Furthermore, multiple vaccine constructs have shown promise8, including two that have an approximately 95% protective efficacy against COVID-199,10. However, these interventions were directed against the initial SARS-CoV-2 virus that emerged in 2019. The recent detection of SARS-CoV-2 variants B.1.1.7 in the UK11 and B.1.351 in South Africa12 is of concern because of their purported ease of transmission and extensive mutations in the spike protein. Here we show that B.1.1.7 is refractory to neutralization by most monoclonal antibodies against the N-terminal domain of the spike protein and is relatively resistant to a few monoclonal antibodies against the receptor-binding domain. It is not more resistant to plasma from individuals who have recovered from COVID-19 or sera from individuals who have been vaccinated against SARS-CoV-2. The B.1.351 variant is not only refractory to neutralization by most monoclonal antibodies against the N-terminal domain but also by multiple individual monoclonal antibodies against the receptor-binding motif of the receptor-binding domain, which is mostly due to a mutation causing an E484K substitution. Moreover, compared to wild-type SARS-CoV-2, B.1.351 is markedly more resistant to neutralization by convalescent plasma (9.4-fold) and sera from individuals who have been vaccinated (10.3-12.4-fold). B.1.351 and emergent variants13,14 with similar mutations in the spike protein present new challenges for monoclonal antibody therapies and threaten the protective efficacy of current vaccines.
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                Author and article information

                Contributors
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                Journal
                Journal of Dental Research
                J Dent Res
                SAGE Publications
                0022-0345
                1544-0591
                July 20 2021
                : 002203452110292
                Affiliations
                [1 ]IrsiCaixa AIDS Research Institute, Badalona, Spain
                [2 ]Dentaid Research Center, Cerdanyola del Vallès, Spain
                [3 ]Catalan Institute of Nanoscience and Nanotechnology, CSIC, and the Barcelona Institute of Science and Technology, Bellaterra (Barcelona), Spain
                [4 ]Germans Trias i Pujol Research Institute, Can Ruti Campus, Badalona, Spain
                [5 ]University of Vic–Central University of Catalonia, Vic, Spain
                Article
                10.1177/00220345211029269
                34282982
                3b302180-637f-42c3-a851-b7ddcbae3b6c
                © 2021

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