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Journal ArticleDOI

The race for coronavirus vaccines: a graphical guide.

28 Apr 2020-Nature (Nature Publishing Group)-Vol. 580, Iss: 7805, pp 576-577
TL;DR: Eight ways in which scientists hope to provide immunity to SARS-CoV-2 .
Abstract: Eight ways in which scientists hope to provide immunity to SARS-CoV-2 . Eight ways in which scientists hope to provide immunity to SARS-CoV-2 .
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Journal ArticleDOI
TL;DR: The mRNA-1273 vaccine induced anti-SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified, which support further development of this vaccine.
Abstract: Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vacci...

2,556 citations

Journal ArticleDOI
TL;DR: It is indicated that healthcare staff involved in the care of COVID-19 positive patients, and individuals considering themselves at risk of disease, were more likely to self-report acquiescence to CO VID-19 vaccination if and when available, and parents, nurses, and medical workers not caring for SARS-CoV-2 positive patients expressed higher levels of vaccine hesitancy.
Abstract: Vaccine hesitancy remains a barrier to full population inoculation against highly infectious diseases. Coincident with the rapid developments of COVID-19 vaccines globally, concerns about the safety of such a vaccine could contribute to vaccine hesitancy. We analyzed 1941 anonymous questionnaires completed by healthcare workers and members of the general Israeli population, regarding acceptance of a potential COVID-19 vaccine. Our results indicate that healthcare staff involved in the care of COVID-19 positive patients, and individuals considering themselves at risk of disease, were more likely to self-report acquiescence to COVID-19 vaccination if and when available. In contrast, parents, nurses, and medical workers not caring for SARS-CoV-2 positive patients expressed higher levels of vaccine hesitancy. Interventional educational campaigns targeted towards populations at risk of vaccine hesitancy are therefore urgently needed to combat misinformation and avoid low inoculation rates.

1,188 citations

Journal ArticleDOI
TL;DR: The primary safety endpoint was adverse reactions within 28 days after injection in all participants who were given at least one dose of study drug (safety population).
Abstract: Summary Background With the unprecedented morbidity and mortality associated with the COVID-19 pandemic, a vaccine against COVID-19 is urgently needed. We investigated CoronaVac (Sinovac Life Sciences, Beijing, China), an inactivated vaccine candidate against COVID-19, containing inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for its safety, tolerability and immunogenicity. Methods In this randomised, double-blind, placebo-controlled, phase 1/2 clinical trial, healthy adults aged 18–59 years were recruited from the community in Suining County of Jiangsu province, China. Adults with SARS-CoV-2 exposure or infection history, with axillary temperature above 37·0°C, or an allergic reaction to any vaccine component were excluded. The experimental vaccine for the phase 1 trial was manufactured using a cell factory process (CellSTACK Cell Culture Chamber 10, Corning, Wujiang, China), whereas those for the phase 2 trial were produced through a bioreactor process (ReadyToProcess WAVE 25, GE, Umea, Sweden). The phase 1 trial was done in a dose-escalating manner. At screening, participants were initially separated (1:1), with no specific randomisation, into two vaccination schedule cohorts, the days 0 and 14 vaccination cohort and the days 0 and 28 vaccination cohort, and within each cohort the first 36 participants were assigned to block 1 (low dose CoronaVac [3 μg per 0·5 mL of aluminium hydroxide diluent per dose) then another 36 were assigned to block 2 (high-dose Coronavc [6 μg per 0·5 mL of aluminium hydroxide diluent per dse]). Within each block, participants were randomly assigned (2:1), using block randomisation with a block size of six, to either two doses of CoronaVac or two doses of placebo. In the phase 2 trial, at screening, participants were initially separated (1:1), with no specific randomisation, into the days 0 and 14 vaccination cohort and the days 0 and 28 vaccination cohort, and participants were randomly assigned (2:2:1), using block randomisation with a block size of five, to receive two doses of either low-dose CoronaVac, high-dose CoronaVac, or placebo. Participants, investigators, and laboratory staff were masked to treatment allocation. The primary safety endpoint was adverse reactions within 28 days after injection in all participants who were given at least one dose of study drug (safety population). The primary immunogenic outcome was seroconversion rates of neutralising antibodies to live SARS-CoV-2 at day 14 after the last dose in the days 0 and 14 cohort, and at day 28 after the last dose in the days 0 and 28 cohort in participants who completed their allocated two-dose vaccination schedule (per-protocol population). This trial is registered with ClinicalTrials.gov, NCT04352608, and is closed to accrual. Findings Between April 16 and April 25, 2020, 144 participants were enrolled in the phase 1 trial, and between May 3 and May 5, 2020, 600 participants were enrolled in the phase 2 trial. 743 participants received at least one dose of investigational product (n=143 for phase 1 and n=600 for phase 2; safety population). In the phase 1 trial, the incidence of adverse reactions for the days 0 and 14 cohort was seven (29%) of 24 participants in the 3 ug group, nine (38%) of 24 in the 6 μg group, and two (8%) of 24 in the placebo group, and for the days 0 and 28 cohort was three (13%) of 24 in the 3 μg group, four (17%) of 24 in the 6 μg group, and three (13%) of 23 in the placebo group. The seroconversion of neutralising antibodies on day 14 after the days 0 and 14 vaccination schedule was seen in 11 (46%) of 24 participants in the 3 μg group, 12 (50%) of 24 in the 6 μg group, and none (0%) of 24 in the placebo group; whereas at day 28 after the days 0 and 28 vaccination schedule, seroconversion was seen in 20 (83%) of 24 in the 3 μg group, 19 (79%) of 24 in the 6 μg group, and one (4%) of 24 in the placebo group. In the phase 2 trial, the incidence of adverse reactions for the days 0 and 14 cohort was 40 (33%) of 120 participants in the 3 μg group, 42 (35%) of 120 in the 6 μg group, and 13 (22%) of 60 in the placebo group, and for the days 0 and 28 cohort was 23 (19%) of 120 in the 3 μg group, 23 (19%) of 120 in the 6 μg group, and 11 (18%) of 60 for the placebo group. Seroconversion of neutralising antibodies was seen for 109 (92%) of 118 participants in the 3 μg group, 117 (98%) of 119 in the 6 μg group, and two (3%) of 60 in the placebo group at day 14 after the days 0 and 14 schedule; whereas at day 28 after the days 0 and 28 schedule, seroconversion was seen in 114 (97%) of 117 in the 3 μg group, 118 (100%) of 118 in the 6 μg group, and none (0%) of 59 in the placebo group. Interpretation Taking safety, immunogenicity, and production capacity into account, the 3 μg dose of CoronaVac is the suggested dose for efficacy assessment in future phase 3 trials. Funding Chinese National Key Research and Development Program and Beijing Science and Technology Program.

1,017 citations

Journal ArticleDOI
TL;DR: The interaction between the viral spike protein and angiotensin-converting enzyme 2, which triggers entry of the virus into host cells, is likely to be involved in the cardiovascular manifestations of COVID-19.
Abstract: Coronavirus disease 2019 (COVID-19), caused by a strain of coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic that has affected the lives of billions of individuals. Extensive studies have revealed that SARS-CoV-2 shares many biological features with SARS-CoV, the zoonotic virus that caused the 2002 outbreak of severe acute respiratory syndrome, including the system of cell entry, which is triggered by binding of the viral spike protein to angiotensin-converting enzyme 2. Clinical studies have also reported an association between COVID-19 and cardiovascular disease. Pre-existing cardiovascular disease seems to be linked with worse outcomes and increased risk of death in patients with COVID-19, whereas COVID-19 itself can also induce myocardial injury, arrhythmia, acute coronary syndrome and venous thromboembolism. Potential drug-disease interactions affecting patients with COVID-19 and comorbid cardiovascular diseases are also becoming a serious concern. In this Review, we summarize the current understanding of COVID-19 from basic mechanisms to clinical perspectives, focusing on the interaction between COVID-19 and the cardiovascular system. By combining our knowledge of the biological features of the virus with clinical findings, we can improve our understanding of the potential mechanisms underlying COVID-19, paving the way towards the development of preventative and therapeutic solutions.

927 citations

Journal ArticleDOI
TL;DR: An artificial intelligence model, which has been trained with tens of thousands of experimental data and extensively validated by experimental results on SARS-CoV-2, reveals that Omicron may be over 10 times more contagious than the original virus or about 2.8 times as infectious as the Delta variant.
Abstract: The latest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant Omicron (B.1.1.529) has ushered panic responses around the world due to its contagious and vaccine escape mutations. The essential infectivity and antibody resistance of the SARS-CoV-2 variant are determined by its mutations on the spike (S) protein receptor-binding domain (RBD). However, a complete experimental evaluation of Omicron might take weeks or even months. Here, we present a comprehensive quantitative analysis of Omicron’s infectivity, vaccine breakthrough, and antibody resistance. An artificial intelligence (AI) model, which has been trained with tens of thousands of experimental data and extensively validated by experimental results on SARS-CoV-2, reveals that Omicron may be over 10 times more contagious than the original virus or about 2.8 times as infectious as the Delta variant. On the basis of 185 three-dimensional (3D) structures of antibody–RBD complexes, we unveil that Omicron may have an 88% likelihood to escape current vaccines. The U.S. Food and Drug Administration (FDA)-approved monoclonal antibodies (mAbs) from Eli Lilly may be seriously compromised. Omicron may also diminish the efficacy of mAbs from AstraZeneca, Regeneron mAb cocktail, Celltrion, and Rockefeller University. However, its impacts on GlaxoSmithKline’s sotrovimab appear to be mild. Our work calls for new strategies to develop the next generation mutation-proof SARS-CoV-2 vaccines and antibodies.

457 citations

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